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1
Fear, Mark William. „Wnt signalling in normal adult epidermis and epidermal tumours“. Thesis, Queen Mary, University of London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406139.
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2
Akinduro, Olufolake A. E. „Autophagy in epidermis“. Thesis, Queen Mary, University of London, 2013. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8703.
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Organ‐transplant recipients (OTRs) on a new class of immunosuppressants, rapamycin and its analogues, have reduced cutaneous Squamous Cell Carcinomas (cSCCs). Rapamycin, an mTORC1 inhibitor, is also a known autophagy inducer in experimental models. Autophagy, which literally means self‐eating, is a cell survival mechanism but can also lead to cell death. Therefore, the main hypothesis behind this work is that rapamycin prevents epidermal tumourigenesis by either affecting epidermal mTOR regulation of autophagy and/or selectively affecting epidermal AKT isoform activity. Epidermal keratinocytes move from the proliferating basal layer upwards to the granular layers where they terminally differentiate, forming a layer of flattened, anucleate cells or squames of the cornified layer which provides an essential environmental barrier. However, epidermal terminal differentiation, a specialised form of cell death involving organelle degradation, is poorly understood. The work presented in this thesis shows that analysis of the autophagy marker expression profile during foetal epidermal development, indicates autophagy is constitutively active in the terminally differentiating granular layer of epidermis. Therefore, I hypothesize that autophagy is a mechanism of organelle degradation during terminal differentiation of granular layer keratinocytes. In monolayer keratinocytes, activation of terminal differentiation is accompanied by autophagic degradation of nuclear material, nucleophagy. This suggests that constitutive autophagy is a pro‐death mechanism required for terminal differentiation. In cultured keratinocytes and in epidermal cultures, rapamycinmediated mTORC1 inhibition strongly increases AKT1 activity as well as up‐regulates constitutive granular layer autophagy promoting terminal differentiation. Therefore, autophagy is an important fundamental process in keratinocytes which may be the mechanism by which terminally differentiating keratinocytes of the epidermal granular layer degrade their organelles required for barrier formation. This may have implications for the treatment of patients with barrier defects like psoriasis. In immunosuppressed OTRs, rapamycin may promote epidermal autophagy and AKT1 activity adding to its anti‐tumourigenic properties.
3
O'Shaughnessy, Ryan Francis Lucas. „Analysis of gene expression in normal and neoplastic keratinocytes“. Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325883.
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4
Gdula, Michal R. „Establishing tissue-specific chromatin organization during development of the epidermis. Nuclear architecture of different layers of murine epidermis and the role of p63 and Satb1 in establishing tissue-specific organization of the epidermal differentiation complex locus“. Thesis, University of Bradford, 2011. http://hdl.handle.net/10454/5382.
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During development, multipotent stem cells establish tissue-specific
programmes of gene expression that underlie a process of differentiation into
specialized cell types.
It was shown in the study that changes in the nuclear architecture during
terminal keratinocyte differentiation show correlation with the dynamics of the
transcriptional and metabolic activity. In particular, terminal differentiation is
accompanied by the decrease of nuclear volume, elongation of its shape,
reduction of the number and fusion of nucleoli, increase in the number of
centromeric clusters and a dramatic decrease of the transcriptional activity.
Global changes in the nuclear architecture of epidermal keratinocytes are
associated with marked remodelling of the higher-order chromatin structure of
the epidermal differentiating complex (EDC). EDC is positioned peripherally in
the epidermal nuclei at E11.5 when its genes show low expression levels and
relocates towards the nuclear interior at E16.5 when EDC genes are markedly
upregulated.
P63 transcription factor serving as a master regulator of epidermal development
is involved in the control of EDC relocation in epidermal progenitor cells. The
epidermis of E16.5 p63KO exhibits significantly more peripheral positioning of
the EDC loci, compared to wild-type.
The genome organizer Satb1 serving as a direct p63 target controls higher
order chromatin folding of the central part of EDC and Satb1 knockout mice
show alterations of epidermal development and expression of the EDC
encoded genes. Thus, this study shows that the programme of epidermal development and
terminal differentiation is regulated by p63 and other factors and include marked
remodelling of three-dimensional nuclear organization and positioning of tissue
specific gene loci. In addition to the direct involvement of p63 in controlling the
expression of tissue-specific genes, p63 via regulation of the chromatin
remodelling factors such as Satb1 promotes establishing specific conformation
of the EDC locus required for efficient expression of terminal differentiation-associated genes.
5
Löwenau, Lilian Julia [Verfasser]. „Human epidermis reconstructed from UV-B irradiated keratinocytes mimics epidermal ageing / Lilian Julia Löwenau“. Berlin : Freie Universität Berlin, 2016. http://d-nb.info/1121588123/34.
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6
Ledesma, Jenilyn A. „A stereological and AgNOR analysis of the epidermis and naevi of Chinese“. Thesis, Hong Kong : University of Hong Kong, 1997. http://sunzi.lib.hku.hk/hkuto/record.jsp?B18656547.
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7
Gdula, Michal Ryszard. „Establishing tissue-specific chromatin organization during development of the epidermis : nuclear architecture of different layers of murine epidermis and the role of p63 and Satb1 in establishing tissue-specific organization of the epidermal differentiation complex locus“. Thesis, University of Bradford, 2011. http://hdl.handle.net/10454/5382.
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During development, multipotent stem cells establish tissue-specific programmes of gene expression that underlie a process of differentiation into specialized cell types. It was shown in the study that changes in the nuclear architecture during terminal keratinocyte differentiation show correlation with the dynamics of the transcriptional and metabolic activity. In particular, terminal differentiation is accompanied by the decrease of nuclear volume, elongation of its shape, reduction of the number and fusion of nucleoli, increase in the number of centromeric clusters and a dramatic decrease of the transcriptional activity. Global changes in the nuclear architecture of epidermal keratinocytes are associated with marked remodelling of the higher-order chromatin structure of the epidermal differentiating complex (EDC). EDC is positioned peripherally in the epidermal nuclei at E11.5 when its genes show low expression levels and relocates towards the nuclear interior at E16.5 when EDC genes are markedly upregulated. P63 transcription factor serving as a master regulator of epidermal development is involved in the control of EDC relocation in epidermal progenitor cells. The epidermis of E16.5 p63KO exhibits significantly more peripheral positioning of the EDC loci, compared to wild-type. The genome organizer Satb1 serving as a direct p63 target controls higher order chromatin folding of the central part of EDC and Satb1 knockout mice show alterations of epidermal development and expression of the EDC encoded genes. Thus, this study shows that the programme of epidermal development and terminal differentiation is regulated by p63 and other factors and include marked remodelling of three-dimensional nuclear organization and positioning of tissue specific gene loci. In addition to the direct involvement of p63 in controlling the expression of tissue-specific genes, p63 via regulation of the chromatin remodelling factors such as Satb1 promotes establishing specific conformation of the EDC locus required for efficient expression of terminal differentiation-associated genes.
8
Raj, N. „Mechanistic studies on the human epidermis“. Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1531697/.
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This thesis is an effort to study the concepts of skin barrier function in relation to skin physiology and biochemistry. The study focused on anatomical differences, effects of photoaging, the sensitivity of skin and pigmentation differences. The most photoexposed area of the skin is the face, so the study was designed to evaluate the factors responsible for barrier function in the facial stratum corneum. Firstly, stratum corneum (SC) protein estimated using a colorimetric assay was compared to the non-destructive Squamescan® method. The study found a good correlation between the two methods for forearm and cheek SC protein. The anatomical differences in relation to filaggrin (filaggrin) degrading proteases bleomycin hydrolase (BH) and calpain-1 (C-1) together with the pyrrolidone carboxylic acid (PCA) were analysed from tape strips of cheek, forearm and leg. The results showed the highest activity of filaggrin degrading proteases in the tapes 4-12. Interestingly, the lowest PCA level was quantified from the cheek, in spite of higher protease activity compared to the other two sites. The next study aimed at understanding the variations of these biomarkers in relation to pigmentation and photodamage. The results showed that the photodamage is associated with a significant decrease in SC barrier function. The study also investigated the role of ethnic differences in SC biochemistry and demonstrated that subjects with the highest level of photodamage had increased levels of plasmin activity and reduced cell maturation. Finally, the last study focused on sensitive skin. Biomarkers were measured in samples taken from the cheek. BH and PCA were found to be lowest in sensitive subjects. The lower corneocyte maturity in the sensitive group was well correlated with the lower transglutaminase activity. This thesis highlights the need to improve NMF levels and the activities of late stage filaggrin degrading enzymes together with a proper differentiation of corneocytes in order to improve the SC barrier. In conclusion, the thesis reports new methods of quantification of the filaggrin degrading enzyme activity, plasmin activity and PCA levels from tape strips. New data have also been generated for variation of these biomarkers in different anatomical sites, ethnicities and skin conditions generated which will provide more information about the molecular biochemistry of SC.
9
Easty, David Julia. „A study of the biochemistry and immunochemistry of differentiation of the normal epidermis and involved psoriatic epidermis“. Thesis, Imperial College London, 1988. http://hdl.handle.net/10044/1/47044.
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10
Harper, Erin Gail. „Adhesion to laminin 5 suppresses p38 map kinase and activating transcription factor 3 in leading keratinocytes of epidermal wounds /“. Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/9299.
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11
Sadowski, Tomasz [Verfasser], Kai [Gutachter] Simons und Michael [Gutachter] Meurer. „Das physiologische Lipidom menschlicher Epidermis : The physiological lipidome of human epidermis / Tomasz Sadowski ; Gutachter: Kai Simons, Michael Meurer“. Dresden : Technische Universität Dresden, 2019. http://d-nb.info/1227196695/34.
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12
Sadowski, Tomasz [Verfasser], Kai Gutachter] Simons und Michael [Gutachter] [Meurer. „Das physiologische Lipidom menschlicher Epidermis : The physiological lipidome of human epidermis / Tomasz Sadowski ; Gutachter: Kai Simons, Michael Meurer“. Dresden : Technische Universität Dresden, 2019. http://d-nb.info/1227196695/34.
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13
Panzer, Rüdiger. „Hautbarrierestörung induziert TLR9-Expression in der Epidermis /“. Kiel, 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000254021.
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14
Gaisford, Wendy Caron. „Aspects of methicillin resistance in Staphylococcus epidermis“. Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302972.
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15
Gumbrys, Aurimas. „Epidermis and re-epithelialization in Schmidtea mediterranea“. Thesis, Open University, 2017. http://oro.open.ac.uk/50972/.
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Epidermal layer is crucial for organism’s survival as its ability to close the wound is essential for tissue recovery. Planarian epidermis enables animal recovery and survival after virtually any body part amputation. Nevertheless, neither the epidermis nor the mechanisms endowing such a remarkable wound healing capacity is described in detail in planarians. Our work introduces live imaging methodology, which allows following epidermal cells and their response to tissue damage or tissue loss for extended time (hours) and in high resolution. Using our methods, we followed planarian cells live for the first time and in conjunction with electron microscopy analysis we described epidermal cell behaviors during tissue maintenance, response to tissue damage and tissue loss. Our data provides comprehensive description of cellular wound response, wound closure as well as preexisting tissue contribution to tissue restoration. In addition, we performed epidermal expression profile analysis to identify the candidate list of epidermally expressed genes to depict the machinery endowing these epidermal cell behaviors. In the pilot functional (RNAi) screen an array of transcription factors with a tissue maintenance phenotypes were identified. Our work established tools for subsequent functional studies of other epidermal expressed genes and paved the way to dissect the mechanisms of the epidermis’ maintenance and efficient wound healing in planarians.
16
Pavlish, John R. „Polymer substrates with microneedles for epidermis injection“. Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/58379.
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Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2009.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 31).
Injections of medicine into the body are commonplace, whether they be intravenous or capsules. The benefit of using a macroneedle for injecting cargo into the circulatory system is its simplicity. However, introduction of the needle intravenously can also include foreign matter if the needle is unsterile. Due to macroneedles ability to pierce skin and veins for effortless insertion, it can also damage unintentional areas if a patient resists the needle, or if it is poorly inserted. Thus the body can be subjected to undesirable materials beyond the intension medicine cargo. Current research reevaluates methods of introducing cargo medicine into the body. Popular models consider polymer substrates with different surface designs and medicine release. Thin polymer substrates allow flexible construction for adhering to tissue while specfic polymers with high Young's modulus create strength for rigidity. Cargo can be placed within or on top of the substrate itself for release to the epidermis or dermis in stages, which is difficult for both oral medicine and macroneedles. A spectic substrate system with microneedles can prevent irflammation or tear of the epidermis but still puncture for cargo release. Depending on the substrate contact surface area, a larger microneedle array can be utilized, for a higher success rate of release beyond individual microneedles. Microneedles can carry and release medicine either internally or externally through the epidermis. In the latter, Langerhans cells can be utilized for activating the immune system by releasing antigenes. Aims of this thesis show the effects of polymer microneedle substrates with methods for constructing the substrate arrays that are flexible adherent to the epidermis, rigid enough for puncturing the stratum corneum, but not weak enough to buckle or be brittle.
by John R Pavlish.
S.B.
17
Blackstock, N. „Factors affecting the structure of salmonid epidermis“. Thesis, University of Stirling, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354053.
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18
Lössner, Isabel. „Die Rolle des bakteriellen Insertionselements IS256 bei der Modulation der Biofilmbildung in Staphylococcus epidermidis“. [S.l. : s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=966050983.
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19
Norlén, Lars Petter Oskar. „The skin barrier : structure and physical function /“. Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3533-5/.
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20
Fairclough, Rebecca J. „Effect of Hailey-Hailey disease mutations on the function of a new variant of human secretory pathway Ca²âº/Mn²âº-ATPase (hSPCA1)“. Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275321.
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21
Chakrabarty, Kaushik H. „Development and evaluation of epidermal/dermal skin composites“. Thesis, University of Sheffield, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273737.
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22
Jones, Keith Thomas. „The role of intracellular calcium in the control of keratinocyte differentiation“. Thesis, University of Liverpool, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359170.
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23
Kettenbach, Arminja Nadine. „Molekulare Mechanismen in Zelldifferenzierung und Zellteilung“. [S.l. : s.n.], 2006.
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24
Pfeiffer, Sven. „Wingless transport in the embryonic epidermis of drosophila“. Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248103.
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25
Silva-Vargas, Violeta. „Characterisation and modulation of patterning of mammalian epidermis“. Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1445848/.
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The epidermis is maintained by proliferation of stem cells and differentiation of their progeny. In my PhD thesis I have studied the mechanisms by which these processes are compartmentalised. P-catenin levels determine lineage commitment in the epidermis. I investigated the role of p-catenin in patterning of the epidermal stem cell compartment and its niche during de novo hair follicle formation. For this I used K14ANP-cateninER transgenic mice. I found that the levels of p-catenin activation determine the number and location of ectopic hair follicles, showing that follicle formation is a threshold-response event. To dissect the downstream effects of p-catenin signalling, I performed microarray analysis and saw that the Hedgehog pathway is upregulated by p-catenin activation. Inhibition of Hedgehog signalling attenuates the effects of p-catenin. The array also revealed that p-catenin regulates the Eph/ephrin protein family. I found that several ephrin-B ligands and EphB receptors are expressed in distinct zones in mouse skin. In order to study the mechanisms modulating epidermal niche patterning I have analysed EphB2, EphB3 and ephrin-B1 null epidermis. EphB/ephrin-B signalling controls hair follicle spacing, patterning along the radial follicle axis, interfollicular epidermal differentiation and melanocyte localisation. Disruption of EphB/ephrin-B signalling disturbs proliferation, uncoupling expression of K15, CD34 and clonal growth capacity. In culture keratinocytes that differ in EphB/ephrin-B expression segregate from one another, reflecting differences in cell shape, motility and integrin expression. EphB3 and ephrin-B1 are induced on activation of p-catenin and augment p-catenin induced cell clustering. Conversely, EphB/ephrin-B signalling negatively regulates p-catenin activation. Ephrin-B/EphB signalling is a key determinant of epidermal pattern, proliferation and differentiation. In summary, I have elucidated the role of p-catenin, Hedgehog and EphB/ephrin-B signalling in regulating epidermal proliferation, differentiation and morphogenesis.
26
Pearton, David Jonathan. „Proprotein convertases in terminal differentiation of epidermis and processing of the profilaggrin amino terminus /“. Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/9230.
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27
Sully, Katherine L. „Inhibition of mammalian target of rapamycin (mTOR) in epidermis“. Thesis, Queen Mary, University of London, 2012. http://qmro.qmul.ac.uk/xmlui/handle/123456789/3360.
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Cutaneous squamous cell carcinoma (cSCC) is one of the most common Caucasian skin cancers and is particularly prevalent following chronic ultraviolet (UV) radiation exposure and in immunosuppressed patients. Recent use of rapamycin as an immunosuppressant significantly reduces SCC after organ transplantation. However the mechanism remains unclear. Rapamycin inhibits mammalian target of rapamycin (mTOR) kinase, downstream from phosphatidylinositol-3 kinase (PI3K) and Akt kinases previously implicated in SCC. The aim was to find the effects of rapamycin on PI3K-Akt-mTOR signalling in epidermis in order to understand rapamycin’s tumour suppressing activity in skin. Rapamycin increases epidermal Akt phosphorylation via inhibition of an mTOR complex 1 (mTORC1)-dependent negative feedback loop to insulin receptor substrate-1. In a skin experimental model, rapamycin selectively increases phosphorylation of Akt1, the epidermal Akt isoform down-regulated in SCC and also down-regulated by UV. Epidermal Akt2, up-regulated in tumours and by UV, is unaffected. Rapamycin enhances restoration of Akt1 phosphorylation in skin recovering from UV radiation, suggesting a mechanism for rapamycin’s anti-tumour activity in epidermis in spite of its efficient immunosuppressive properties. As rapamycin targets mTORC1, newer classes of mTOR inhibitors active against mTORC1 and mTORC2 are under development. While comparing the two drug classes it was found that rapamycin unexpectedly increases epidermal mTORC2 activity. Since mTORC2 signalling influences lipid synthesis and epidermis requires extensive lipogenesis for formation of its protective barrier, the relationship between epidermal mTORC2 signalling, lipogenesis and barrier to UV was explored. Rapamycin increased epidermal lipid levels, but this increase was not sufficient to protect against UV-induced DNA damage. 3 In conclusion, rapamycin treatment can increase PI3K/Akt1 and mTORC2 signalling and lipid levels in epidermis. Rapamycin can increase epidermal Akt1 phosphorylation during UV recovery, which may contribute to the anti-cancer action of rapamycin in skin. Rapamycin’s potential to increase epidermal lipid levels makes it an interesting possible therapeutic for treating skin disorders with dyslipidemia.
28
Spencer, Mary-Jane. „The influence of ultraviolet B radiation on human epidermis“. Thesis, University of Edinburgh, 1994. http://hdl.handle.net/1842/20808.
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The aim of this work was to study the relationship between UVB and LC by examining the influence of moderate, suberythemal doses of UVB, such as are used to treat psoriasis, on epidermal LC morphology, numbers and surface expression of CD1a and major histocompatibility class II (MHC II) antigens in human skin. A six week course of UVB irradiation, using our standard therapeutic regimen for the treatment of psoriasis (total doses of UVB ranged from 2.58-5.58 J/cm2), was administered to nine healthy subjects. The morphology and number of LCs, and the distribution and expression of certain LC surface antigens were studied in control and in UVB-irradiated epidermis. The study of LC morphology prior to UVB irradiation, using the technique of confocal laser scanning microscopy, revealed that their dendrites extended mainly in the horizontal plane of the epidermis and dendrite numbers ranged between two and nine per cell. Adjacent LCs were in close apposition, but there was little contact between them The majority of normal unirradiated epidermal LCs expressed HLA-DP, HLA-DQ and HLA-DR antigens, which were demonstrated by quantitative ultrastructural immunogold method using image analysis, although a small proportion either did not express these antigens or expressed them at high surface densities. In conclusion, a true reduction in the number of LCs occurs after UVB exposure which cannot be explained simply by the loss of LC surface antigen expression. These studies have defined the UVB-induced changes in LC morphology, number and antigen expression in normal human skin.
29
Enikanolaiye, Adebola. „The Role of the Claudin 6 Cytoplasmic Tail In Epidermal Differentiation and the Role of Cdx In Endodermal Development“. Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32354.
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The mammalian skin provides a necessary barrier between the organism and the environment, defending against loss of water and solutes, preventing the invasion of pathogens as well as protecting against chemical and physical assault. Claudin (Cldn)-based Tight Junctions (TJs) are the main functional part of the skin barrier. In particular, Cldn6 through its cytoplasmic tail has been shown to be important for barrier function. In other to further investigate the role of the Cldn6 tail in TJ-function, we developed Cldn6 mouse mutants carrying varying truncations of the Cldn6 tail. Both of these mice present with epidermal differentiation perturbations and delayed barrier function that is repaired later in life. These studies support the importance of the tail portion of the Cldn molecules in epidermal differentiation and barrier function. In addition, both of these mouse models are useful for the study of barrier function in preterm infants and in aging, with the hope of developing novel therapeutics for the alleviation of barrier dysfunction.
Cdx is a family of homeodomain (HD) transcription factors (TFs) essential for many key developmental processes. In particular, Cdx2 is important for the establishment and maintenance of posterior identity in the developing endoderm. In spite of this, only a few Cdx targets in the developing endoderm have been discovered. In addition, the interplay between Cdx and its targets within the endoderm is poorly understood. In this study, we show that the forkhead box transcription factor, Foxa2 is a Cdx2 target. We also show that Foxa2 and Cdx2 physically and genetically interact to regulate a subset of genes that are implicated in endodermal development. These studies help to further our understanding of endoderm biology with the goal of developing new strategies to diagnose and treat diseases associated with defective endoderm development.
30
Souto, Luis Ricardo Martinhão. „Modelo de pele humana (derme + epiderme) reconstruida in vitro“. [s.n.], 2005. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313309.
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Orientador: Maria Beatriz Puzzi, Maria Helena Stangler KraemerDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-04T03:54:34Z (GMT). No. of bitstreams: 1 Souto_LuisRicardoMartinhao_M.pdf: 2402921 bytes, checksum: a79b6ae181ce1b24d01ec608815d8bf7 (MD5) Previous issue date: 2005
Resumo: A obtenção de uma pele humana que apresente derme e epiderme, reconstruída a partir de células isoladas de pacientes, possibilita a realização de enxertos autólogos de pele reconstruída em laboratório (in vitro) em pacientes com áreas doadoras escassas além de permitir ensaios com substâncias químicas e drogas in vitro e não mais in vivo. A partir da cultura de fibroblastos humanos, é possível obter um número suficiente de células que podem ser injetadas em uma matriz de colágeno bovino tipo I que, mantida imersa em meio de cultura, específico para fibroblastos, permite a formação de uma derme humana reconstruída in vitro. Sobre essa derme, através de cultura de queratinócitos e melanócitos humanos, forma-se uma epiderme diferenciada levando à formação de uma pele humana reconstruída in vitro, constituída de derme e epiderme associadas. Essa pele humana formada é, histologicamente, semelhante à pele humana in vivo. Na derme, identifica-se o tecido colágeno, com suas células, e a matriz extracelular organizados paralelamente à epiderme. Esta se desenvolve em várias camadas. Não há distinção entre derme e epiderme no experimento controle, onde não foi utilizado o colágeno bovino tipo I
Abstract: The technique to obtain human skin presenting dermis and epidermis reconstructed from cells isolated from patients allows the performance of autologous grafts of skin reconstructed in laboratory (in vitro) on patients with scarce donor sites, in addition to permitting trials with chemical substances and drugs no more in vivo, but in vitro. It is possible to obtain a sufficient number of cells from human fibroblast culture that can be injected in bovine collagen type I matrix and kept submerged in a specific culture medium for fibroblasts. This will permit the formation of human dermis reconstructed in vitro. On this dermis, through culture of human keratinocytes and melanocytes, a differentiated epidermis is formed, leading to the creation of human skin reconstructed in vitro, composed of associated dermis and epidermis. This human skin is histologically formed in the same way as human skin in vivo. Collagen tissue can be identified in the dermis, with its cells and extracellular matrix organized in parallel to the epidermis, which is developed in several layers
Mestrado
Patologia Clinica
Mestre em Ciências Médicas
31
Koster, Jan Johannes Bernardus. „Plakin interactions in the hemidesmosome“. [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2003. http://dare.uva.nl/document/69999.
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32
Boudonck, Kurt. „Dynamic organization of transcription and transcript processing components in plants“. Thesis, University of East Anglia, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302341.
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33
Carpenter, Kevin Joseph. „Structure and evolution of the leaf epidermis in basal angiosperms /“. For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2005. http://uclibs.org/PID/11984.
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34
Welss, Thomas. „Molekularbiologische Untersuchungen differenziell exprimierter Gene in Tumoren der humanen Epidermis“. [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=965458849.
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35
Panchal, Heena. „Neuregulin3 alters cell fate in the epidermis and mammary gland“. Thesis, Institute of Cancer Research (University Of London), 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.498460.
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36
Hwang, Hwei-tein. „Characterisation of cDNA clones for mRNAs expressed in leaf epidermis“. Thesis, University of Nottingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289432.
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37
Lowell, Sally Elizabeth. „Delta and the fate of stem cells in human epidermis“. Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402134.
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38
Nuttall, A. „The role of the epidermis in pathogenesis of systemic sclerosis“. Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/19394/.
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Studies into the pathogenesis of systemic sclerosis (SSc) skin fibrosis to date have concentrated on dermal changes in the disease. Little attention has been paid to the epidermis in SSc. Epithelial-fibroblast interactions are believed to regulate wound healing and contribute to a number of fibrotic diseases. Recent proteomic data from our laboratory reveals altered keratinocyte (KC) specific proteins in SSc skin consistent with a wound healing phenotype of the disease epidermis. I therefore studied SSc KCs focusing on differentiation and KC-fibroblast interaction. I found that KC maturation is altered in SSc with abnormal persistence of cytokeratins 1, 10 and 14 into suprabasal layers. Cytokeratins 6 and 16, induced in wound healing KCs, were shown to be expressed in SSc epidermis. In addition, IL-1, a pivotal cytokine involved in KC and fibroblast events post epidermal injury, and its downstream signalling phosphoproteins p38 and JNK were elevated in SSc epidermis. I went on to study the effect of SSc epidermis on normal human fibroblasts. I found that SSc epidermis promoted fibroblast activation in an ET-1, TGF-β, and IL-1 dependent fashion. I suggest a double paracrine loop initiated by KC-derived IL-1 as a mechanism for epidermal-dermal co-activation in the disease, similar to that previously demonstrated for wound healing. There is a need for developing antifibrotic agents targeting epithelium-derived factors and their signalling pathways. I went on to study normal epidermal wound healing. A paradox during epithelial repair is that KCs proliferate despite a TGF-β dominated environment, which is known to be anti-proliferative. Our laboratory previously showed that prostanoids antagonise TGF-β-dependent events in human cells. The induction of prostanoids following injury could transiently free KCs from the anti-proliferative effects of TGF-β. I test this hypothesis by confirming transient induction of epidermal COX II and PGE2 following injury. I also show that PGE2 antagonises the anti-proliferative and pro-migratory effects of TGF-β on KCs. My work supports a model where induction of epidermal wound edge COX II leads to antagonism of TGF-β and allows KCs to proliferate prior to migration over the wound.
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Wang, Sha. „The Apicobasal Polarity Protein Network during Stratified Xenopus Epidermis Development“. University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1397736009.
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Pyee, Jaeho. „Isolation and characterization of plant epidermis-specific proteins and genes /“. The Ohio State University, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487853913103024.
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Gallagher, Kimberly L. „Analysis of asymmetric cell divisions in the maize leaf epidermis /“. Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2000. http://wwwlib.umi.com/cr/ucsd/fullcit?p3007134.
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Terzi, Rodríguez Denise Andrea. „Caracterización Anatómica de la Epidermis Foliar en Sequoia sempervirens (D. Don)“. Tesis, Universidad de Chile, 2008. http://repositorio.uchile.cl/handle/2250/105013.
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Vorstenbosch, Joshua. „Overexpression of CD109 in the epidermis reduces skin fibrosis and inflammation“. Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116840.
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Transforming growth factor-beta (TGF-ß) is a multifunctional growth factor involved in a variety of cellular processes including wound healing, extracellular matrix deposition, inflammation, and fibrosis. Excessive TGF-ß signaling during wound healing causes sustained inflammation and elevated expression of extracellular matrix proteins, which have both been associated with fibrosis and scarring. Therefore, inhibition of TGF-ß during wound healing is an attractive target to reduce fibrotic skin disorders. Our lab is interested in CD109, a 150 kDa GPI-anchored protein which has been shown to bind TGF-ß in its soluble form and to inhibit TGF-ß signaling in keratinocytes and fibroblasts in vitro. The TGF-ß antagonist properties of CD109 suggest that modulation of its expression in vivo might ameliorate fibrosis and scarring, perhaps via differential activation of keratinocytes and fibroblasts. To investigate the role of CD109 in the skin, we generated transgenic mice overexpressing CD109 in the epidermis.To explore the role of CD109 during wound healing, I conducted incisional and excisional wound healing studies using CD109 transgenic mice and wild-type littermate controls. These studies demonstrate improved scarring parameters including reduced myofibroblast differentiation, reduced granulation tissue, and improved extracellular matrix architecture in the CD109 transgenic mice. Additionally, the data in this thesis show that overexpression of CD109 in the epidermis inhibits immune cell recruitment, and is associated with a reduction in expression of the proinflammatory cytokines IL-1 and MCP-1. I correlated these data with immunohistochemical analysis of Smad2/3 phosphorylation, and show that CD109 overexpression is associated with a reduction in TGF-ß signaling. Collectively, these data suggest that overexpression of CD109 in the epidermis inhibits fibrosis during wound healing in a TGF-ß dependent manner.To better understand the role of CD109 in fibrosis, I employed a murine bleomycin-induced model of fibrosis, which exhibits similarities to scleroderma, in CD109 transgenic mice and wild-type littermates. This study shows that CD109 transgenic mice express reduced levels of the extracellular matrix proteins fibronectin and collagen I, as well as Smad2/3 phosphorylation, and also display improved extracellular matrix architecture and reduced dermal thickness. Collectively, these data suggest that CD109 resists bleomycin-induced fibrosis, and could thus be an attractive target for therapeutic treatment of fibrotic skin disorders.To better understand how CD109 modulates TGF-ß in vivo, I analyzed the TGF-ß signaling molecules in skin, primary keratinocytes, and primary fibroblasts harvested from CD109 transgenic mice and wild-type littermates. Here, I show that CD109 transgenic mice express less collagen I and fibronectin, and display elevated ALK1 expression and signaling through the Smad1/5/8 pathway while wild-type mice express elevated ALK5 and preferentially signal through the Smad2/3 pathway. Investigation of cultured keratinocytes showed a similar expression pattern, with the only difference existing in the expression of ALK1 and ALK5 which were both increased in the CD109 transgenic keratinocytes, and fibroblasts from both genotypes showed similar expression patterns. In both cultured keratinocytes and whole skin extracts, the CD109 transgenic tissue expressed less TGF-ß than their wild-type counterparts. The differential TGF-ß signaling described here could underscore our previous observations indicating that overexpression of CD109 inhibits scarring and fibrosis in vivo.Collectively, the data presented here demonstrate that CD109 potently alters physiological processes in the skin in vivo. The capacity for CD109 to reduce scarring, fibrosis, and inflammation in vivo makes it an attractive target for treating fibrotic skin disorders.Le facteur de croissance transformant bêta (TGF-ß), est un facteur de croissance multifonctionnel impliqué dans une multitude de processus cellulaires tel que la cicatrisation, la déposition de matrice extracellulaire, l'inflammation et la fibrose. Ainsi, l'inhibition de TGF-ß semble être une cible de choix pour réduire les désordres fibrotiques de la peau. Notre laboratoire a identifié CD109, une proteine de 180 kDa ancrée à un glycosylphosphatidylinositol agissant comme co-récepteur cellulaire de TGF-ß. Ce nouveau récepteur, auquel TGF- ß s'ancre avec très haute affinité, aurait pour propriété d'inhiber la signalisation intra-cellulaire de TGF-ß. Les propriétés antagonistes de CD109 suggèrent que la modulation de son expression in vivo dans la peau pourrait améliorer la cicatrisation et la fibrose cutanée. Pour investiguer le role de CD109 dans la peau, nous avons généré une souris transgénique en clonant CD109 en aval du promoteur de keratin-14, limitant ainsi la surexpression de CD109 à l'épiderme.Afin d'explorer le rôle de CD109 au sein de la guérison des plaies, nous avons conduit des études de ce processus où nous avons pu observer une amélioration des paramètres de cicatrisation tels que la réduction de la différentiation des myofibroblastes, la réduction du tissu de granulation et une amélioration de l'architecture de la matrice extracellulaire chez les souris transgénique CD109 comparées au souris de génotype sauvage pour la même portée. De plus, la surexpression de CD109 dans l'épiderme inhibe le recrutement de cellules immunitaires au site de la plaie et est associé avec une réduction de la signalisation de TGF-ß ainsi que l'expression des cytokines pro-inflammatoire IL-1 et MCP-1. Toutes ces données, suggèrent que la surexpression de CD109 dans l'épiderme inhibe la fibrose cutanée lors de la guérison des plaies.Nous avons ensuite examiné le rôle de CD109 lors de la fibrose en utilisant un model de sclérodermie murine induit par bleomycine. La souris transgénique CD109 exprime des niveaux réduits des protéines fibronectine et collagène 1 dans la matrice extracellulaire, ainsi que des niveaux réduits de phosphorylation de Smad2/3. Elle démontre aussi une meilleure architecture de la matrice extracellulaire et une réduction de l'épaisseur de la couche dermique. Toutes ces données suggèrent que CD109 résiste à la fibrose induite par bleomycine. Cela pourrait donc en faire une cible attrayante pour traitement thérapeutique des désordres fibrotiques de la peau.Pour mieux comprendre comment CD109 modifie l'action de TGF-ß in vivo, nous avons analysé les molécules de signalisation de TGF-ß dans la peau, les keratinocytes primaires et les fibroblastes primaires récoltés des souris transgéniques et de leur sœurs de portée du génotype sauvage. Les souris transgéniques CD109 expriment substantiellement moins de collagène I, de fibronectine et démontre une expression élevée de ALK1 et une activation élevée de la voie Smad1/5/8. Les études utilisant des keratinocytes cultivés démontrent une phosphorylation de Smad et une expression des gènes de la matrice extracellulaire similaire; l'expression de ALK1 et ALK5 étant toutefois plus élevée dans les keratinocytes transgéniques CD109 comparé à ceux du génotype sauvage. Les fibroblastes des deux génotypes démontrent des profils d'expression similaires. La signalisation différentielle de TGF-ß pourrait rehausser nos observations précédente et ainsi renforcer l'idée que la surexpression de CD109 inhibe la cicatrisation et la fibrose cutanée in vivo.Ainsi, les données présentée démontrent que CD109 est un puissant altérateur des processus physiologiques de guérison des plaies, cicatrisation, fibrose et inflammation dans la peau in vivo. La capacité pour CD109 de réduire la cicatrisation, la fibrose et l'inflammation dans la peau in vivo en font une cible attrayante pour traiter les désordres fibrotiques de la peau.
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Courtney, Alan Peter. „The role of innexins in the embryonic epidermis of Drosophila melanogaster“. Thesis, University of Sussex, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413334.
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FREZZA, VALENTINA. „Role of TG3 in the protection of epidermis from UVB photodamage“. Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2015. http://hdl.handle.net/2108/202954.
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La transglutaminasi 3 è una proteina solubile che appartiene a un’importante famiglia di enzimi dipendenti dal Ca2+, che catalizzano diversi tipi di modificazioni post-traduzionali. La più studiata e nota reazione catalizzate dalle transglutaminasi è il legame crociato tra proteine. La generazione di legami covalenti ε(γ-glutamil)lisina tra polipeptidi adiacenti oppure intracatena, permette la stabilizzazione di complessi proteici durante vari processi cellulari. La famiglia delle transglutaminasi include nove membri, di cui tre (TG1, TG3 e TG5) sono espressi nella pelle durante il differenziamento dei cheratinociti. Questo processo è noto come cornificazione e rappresenta un modello esclusivo di differenziamento e morte cellulare programmata. Durante la cornificazione, la TG3 è attivata tramite proteolisi, che le permette di cooperare con la TG1 nell’assemblaggio e il rinforzo dello strato corneo. La TG3 catalizza la formazione di legami crociati di diverse proteine strutturali, tra cui la loricrina, le small proline-rich proteins e la tricoialina. Nel nostro lavoro, abbiamo caratterizzato un nuovo modello di topo knockout per TGM3 (TG3KO), il gene codificante la TG3. Nonostante i topi non esprimenti la TG3 presentino un fenotipo apparentemente normale, abbiamo scoperto che nella loro epidermide c’è un’alterazione dell’espressione dei marcatori tardivi del differenziamento cheratinocitico. Avendo anche dimostrato che i corneociti estratti dall’epidermide dei topi TG3KO sono più suscettibili alla disintegrazione cellulare con ultrasuoni (sonicazione) rispetto ai WT, abbiamo ipotizzato che i topi TG3KO potessero essere più sensibili all’apoptosi indotta da irradiazione UVB, per via di una ridotta capacità filtrante dello strato corneo. Con i nostri esperimenti, abbiamo quindi provato che I’assenza della TG3 causa una maggiore formazione di dimeri di pirimidine a seguito dell’irradiazione con UVB di topi neonati di 5 giorni di età. L’esteso danno al DNA fa sì che, di conseguenza, nell’epidermide dei topi TG3KO sia presente anche un maggior numero di cellule apoptotiche. Tali dati sono stati confermati dal rilevamento di un cospicuo livello di caspasi 3 attiva e di cellule TUNEL-positive nell’epidermide dei topi TG3KO rispetto ai WT. In conclusione, i nostri risultati indicano che il legame crociato dei precursori dell’involucro corneo mediato dalla TG3 contribuisce in maniera importante alla funzione protettiva dello strato corneo dagli UVB. Questa nuova evidenza potrebbe anche spiegare il motivo per il quale la TG3 è inclusa tra i fattori prognostici e i candidati soppressori tumorali dei tumori umani della testa e del collo.Transglutaminase (TG3) is a soluble protein that belongs to an important family of Ca2+-dependent enzymes responsible for protein cross-linking. Transglutaminases stabilize protein assemblies by catalysing the formation of intra- or intermolecular Nε(γglutamyl)lysine bonds between adjacent polypeptides. TGs family includes nine members, among them three (TG1, TG3 and TG5) expressed in the skin during keratinocyte differentiation. This process is an exclusive model of terminal differentiation and programmed cell death, also known as cornification. During cornification, TG3 undergoes to proteolytic activation resulting in high cross-linking activity enzyme. It cooperates with TG1 for the assembly and the reinforcement of the stratum corneum, by catalysing the cross-linking of several structural proteins, including loricrin, small proline-rich proteins, and trichohyalin. In our study, we characterized a novel TG3-deficient mouse. TG3-depleted mice have normal gross morphology, but we identified an altered expression of the late differentiation markers in the TG3KO epidermis. Since CEs isolated from TG3KO epidermis are more susceptible to sonication than WT, we hypothesized that TG3KO mice could be more sensitive to apoptosis induced by UVB than WT mice, due to the decreased UVBfiltering capacity of the stratum corneum. We found that the skin of TG3-deficient mice is high sensitive to the formation of cyclobutane pyrimidine dimers after UVB irradiation of new-born mice skin, leading to increased level of UVB-induced cell death. This data have been confirmed by a stronger activation of the caspase 3 and a higher amount of TUNEL-positive cells in irradiated TG3KO skin. Our results indicate that TG3 strongly contributes to the protective function of the stratum corneum from UVB, by reinforcing CEs adding specific crosslinks. This novel finding could explain the reason for including TG3 among candidate tumour suppressor genes in human head and neck cancers.
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Wood, Julian Lawrence. „The role of pH signalling in stomatal responses“. Thesis, University of Oxford, 1996. https://ora.ox.ac.uk/objects/uuid:e97ed751-5a06-4bc7-9a48-d09b8a93d9a8.
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The role of cytoplasmic pH in guard cell signal transduction was investigated in epidermal strips of Commelina communis. The cytoplasmic pH of guard cells was measured by dual excitation ratio confocal laser scanning microscopy. Large transient alkalinisations occurred for up to 20 minutes both during closure, in response to ABA and calcium, and opening in response to IAA and fusicoccin. Therefore the direction of the pH change does not determine the direction stomatal movement in Commelina communis in contrast to previous reports in Paphiopedilum tonsum. Furthermore, CO2 caused a slow acidification during stomatal closure, indicating that pore movements are not always associated with a transient cytoplasmic alkalinisation. The internal pH of guard cells was buffered by low concentrations of isobutyrate. Small reductions in stomatal closure in response to ABA and calcium were observed, however, responses to CO2, IAA and fusicoccin were unaltered. High levels of isobutyrate stimulated wide stomatal opening for all stimuli. Therefore manipulation of cytoplasmic pH only give limited support in the case of ABA and calcium that cytoplasmic pH changes are either necessary for or modulate stomatal movements. The observed pH changes may therefore be a consequence of the mechanism underlying pore movement rather than genuine cytoplasmic signals per se, A model is described based on strong ion and weak acid chemistry which predicts that the observed pH transients result from changes in the concentrations of chloride and malate which charge balance the potassium fluxes during stomatal movements. No suitable fluorescent indicator was found to measure pH in either the apoplast or vacuole. However the volume of the guard cell lumen, vacuole, nucleus and chloroplast were directly measured during stomatal movements and the cytoplasmic volume was calculated. These volumes were used to re-calculate compartmental pH and ion concentrations from previous reports.
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Owen, Markus Roger. „Mathematical modelling of the macrophage invasion of tumours and juxtacrine signalling in epidermal wound healing“. Thesis, University of Warwick, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.344031.
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Larivière, Nathalie. „Integral Roles for the Tight Junction Protein Claudin-6 in Regulating Epidermal Homeostasis“. Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/30650.
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Forming and maintaining an intact epidermal permeability barrier (EPB) is necessary to mammalian health and dysregulation of this process can result in serious complications. Tight junctions (TJs) and their integral proteins the Claudins (Cldns) have both structural and signaling importance to the skin barrier and the latter is most likely mediated via Cldn tail interaction with cytoplasmic proteins. Given that the family member Cldn6 is known to be important to EPB function, we set out to determine the contribution of its cytoplasmic tail domain to TJ-mediated homoeostasis.
Using transgenic mouse models, we overexpressed epidermal-targeted tail truncation mutants and assessed EPB formation and maintenance. We then used yeast 2-hybrid and quantitative proteomic approaches to identify proteins that interact with this tail region and to assess the downstream effects of overexpressing these proteins in human keratinocytes in culture.
We demonstrate that a 10 amino acid region in the cytoplasmic tail is required for efficient epidermal maturation and injury repair and that our mouse models may be applicable to postnatal epidermal maturation and human skin aging studies. We show that in addition to the known interacting partner ZO1, the C-terminal tail of Cldn6 also binds FIZ1 (Flt3 interacting zinc finger protein-1), which we characterize for the first time as a mitogenic factor for keratinocytes. FIZ1 stimulates autocrine pathways involving secreted heparin-binding factors IGFBP3 and DKK1, sensitization to IGF signaling, MAP/ERK activation and increased G1 progression. Specific transcription factors, protein kinases and signaling scaffolds that we identified as novel FIZ1-binding partners likely mediate this signaling.
Our studies on the Cldn6 cytoplasmic tail support the importance of this region for epidermal maturation and for maintenance of skin homeostasis throughout life. They also delineate the potential for tail interactors such as ZO1 and FIZ1 to act in concert with Cldns in TJ-based signaling networks to regulate the balance between proliferation and differentiation in keratinocytes. These findings provide new insight into the role of the Cldn6 cytoplasmic tail and will ultimately aid in the development of new diagnostic tools and therapeutic approaches for the treatment of skin conditions rooted in barrier defects.
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Tan, Wei Min. „Single cell gene expression profiling of human epidermal keratinocytes“. Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609685.
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Lübbe, Katharina. „Entwicklung und Einsatz eines In-vitro-Ischämiemodels zur Untersuchung zellulärer Pathomechanismen der Klauenrehe des Rindes“. Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-171594.
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Die subklinische Klauenrehe oder claw horn disruption (CHD) ist von großer wirtschaftlicher Bedeutung für die Rinderhaltung, da sie zu Lahmheiten, Beeinträchtigungen des Allgemeinbefindens sowie einer eingeschränkten Leistungsfähigkeit der Tiere führt. Trotz zahlreicher Untersuchungen sind die pathophysiologischen Grundlagen der CHD noch immer nicht vollständig geklärt. Die derzeitigen Hypothesen weisen auf eine Ischämie in den noch lebensfähigen Epidermisschichten infolge einer veränderten dermalen Mikrozirkulation. Diese hat pathophysiologische Veränderungen zur Folge, die eine Störung der epidermalen Zellproliferation, eine Schädigung der dermo-epidermalen Verbindung sowie eine veränderte Keratinisierung und Hornproduktion umfassen. Von Bedeutung sind daher In-vitro-Ischämiemodelle, um die epidermale Reaktionsmechanismen auf die pathologischen Veränderungen der Dermis zu untersuchen. Ziel in der vorliegenden Arbeit war die Etablierung eines In-vitro-Ischämiemodells auf der Grundlage boviner Keratinozyten aus der Klauenepidermis. Mithilfe dieses Modells sollten die zellulären Pathomechanismen infolge einer Ischämie, einer Hypoxie sowie eines Glukoseentzugs untersucht werden. Des Weiteren stand die Analyse des Differenzierungsverhaltens der Keratinozyten infolge ischämischer, hypoxischer und hypoglykämischer Konditionen im Mittelpunkt. Für die Etablierung des In-vitro-Ischämiemodells diente als Grundlage das oxygen glucose deprivation (OGD)-Modell, das die Untersuchung eines gleichzeitigen Sauerstoff- und Glukosemangels sowie lediglich einer Hypoxie und eines Glukoseentzugs bei bovinen Keratinozyten ermöglichte. Die Versuche wurden in eine Kurzzeitanalyse über 96 Stunden sowie eine Langzeitanalyse über drei Wochen geteilt. Nach erfolgter Exposition wurde die Zellviabilität mittels LDH(Lactatdehydrogenase)- und MTT(3-(4,5-Dimethylhiazol-2-yl)-2,5-diphenyltetrazoliumbromid)-Assay untersucht. Des Weiteren wurde das veränderte Differenzierungsverhalten der Keratinozyten infolge der veränderten Kultivierungsbedingungen mittels Western Blot-Analyse anhand der Involukrin- und Lorikrin-Expression untersucht. Die Keratinozyten zeigten infolge einer OGD nach kurzer Expositionsdauer die höchsten zytotoxischen Effekte, die von einer zeitabhängigen Abnahme der Zellviabilität sowie massiven morphologischen Veränderungen gefolgt wurde. Hypoxische Bedingungen bewirkten eine zeitabhängige Abnahme der Zellviabilität, die erst nach zweiwöchiger Inkubation die größte Zytotoxizität aufwies, sowie eine geringgradig veränderte Zellmorphologie bei Erhaltung des Zellverbands. Der Glukoseentzug bewirkte eine stark verminderte Zellviabilität sowie starke morphologische Zellveränderungen. In der Western Blot-Analyse konnte eine gesteigerte Involukrin- und Lorikrin-Expression infolge einer OGD, einer Hypoxie und eines Glukoseentzugs nachgewiesen werden. In der vorliegenden Arbeit konnte erstmalig ein auf bovinen Keratinozyten basierendes In-vitro-Ischämiemodell etabliert werden, das die Untersuchung zellulärer Mechanismen der Epidermis ermöglichte. Die OGD zeigte den stärksten Einfluss auf die Zellviabilität sowie eine veränderte Zelldifferenzierung der Keratinozyten, was die pathophysiologischen Veränderungen im Rahmen der CHD reflektiert. Die ebenfalls starken Zellveränderungen infolge eines Glukoseentzugs verdeutlichen die Rolle der Glukose im Zellmetabolismus der Keratinozyten. Solch ein epidermaler Glukosemangel ist in Verbindung mit der negativen Energiebilanz der Rinder im peripartalen Zeitraum denkbar. Die Ergebnisse infolge einer Hypoxie verweisen auf vielfältige Adaptationsmechanismen der Keratinozyten an hypoxische Bedingungen, denen sie in der Epidermis in vivo während der Zelldifferenzierung ausgesetzt werden. Damit besitzt das In-vitro-Ischämiemodell ein großes Potenzial für den Einsatz in der Klauenreheforschung, um einerseits die mit einer Ischämie einhergehenden pathologischen Veränderungen der CHD untersuchen zu können. Andererseits liefert das Modell wertvolle Informationen zu den physiologischen Grundlagenmechanismen der Epidermis, die mit der Zelldifferenzierung einhergehenThe subclinical laminitis or claw horn disruption (CHD) is of great economic importance in the dairy industry as it causes lameness, poor general condition and reduced performance. Despite extensive research efforts, the pathomechanism of CHD remains widely unclear. The current hypotheses on CHD pathogenesis include ischemic alterations of the epidermal keratinocytes resulting from an impaired blood supply. This causes an alteration of cell proliferation, a dermo-epidermal separation and an impaired keratinization and horn production. Therefore, in vitro ischemia models are of critical importance in clarification of the epidermal responses to an altered microcirculation. The aim of this study was the establishment of an in vitro ischemia model based on bovine claw keratinocytes. This in vitro model should enable the investigation of cellular pathomechanisms following exposure to ischemia, hypoxia and glucose deprivation. An additional aim was the analysis of the differentiation pattern of keratinocytes under ischemic, hypoxic and hypoglycaemic conditions. To establish the in vitro ischemia model, the keratinocytes were exposed to oxygen-glucose deprivation (OGD). In addition, this model allowed the parallel examination of hypoxic and hypoglycaemic conditions on bovine claw keratinocytes. The experiments were divided into a short-term analysis over 96h and a long-term analysis over three weeks. Measurement of cell viability was performed by LDH(lactatedehydrogenase) and MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra- zolium bromide) assays. Furthermore, the differentiation pattern of the keratinocytes after exposure to ischemia, hypoxia and glucose deprivation was detected by western blot analysis of the focus on expression of involucrin and loricrin. The highest cytotoxic effect was measured after short exposure to OGD followed by a time-dependent decrease of cell viability and extensive morphological changes of the keratinocytes. Hypoxic conditions lead to a time-dependent decrease of cell viability with the highest cytotoxicity after two weeks. The keratinocytes showed slight changes in cell morphology while maintaining a confluent cell layer. Exposure of keratinocytes to glucose deprivation showed a high decrease of cell viability and strong morphological changes. Furthermore, western blot analysis showed an altered expression pattern with increased involucrin and loricrin levels after exposure to OGD, hypoxia and glucose deprivation. The present study established for the first time an in vitro ischemia model based on bovine claw keratinocytes to study the cellular mechanisms of the epidermis. After exposure to OGD, keratinocytes showed the highest loss in cell viability and an altered cell differentiation. This reflects the pathophysiological changes following epidermal ischemia occurring during the pathogenesis of CHD. The massive cellular alterations after glucose deprivation provide good evidence for the importance of glucose in the cellular metabolism of keratinocytes. An epidermal glucose deficiency may occur in combination with a negative energy balance during peripartal period in cattle. The results of hypoxia show the different adaptive mechanisms of keratinocytes to hypoxic conditions which are present in the epidermis during cell differentiation. Thus, the in vitro ischemia model has a great potential for use in research into CHD pathogenesis and pathomechanisms associated with ischemia. On one side, it is possible to investigate the pathological changes following ischemia during CHD. On the other side, the model offers useful information on physiological response mechanisms of the epidermis that correlate with cell differentiation