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Dynamics of cell-cell junctions in keratinocytes

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Please use this identifier to cite or link to this item: http://hdl.handle.net/1928/12630

Dynamics of cell-cell junctions in keratinocytes

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dc.contributor.author Chavez, Miquella
dc.date.accessioned 2011-06-03T17:27:14Z
dc.date.available 2011-06-03T17:27:14Z
dc.date.issued 2011-06-03
dc.date.submitted July 2009
dc.identifier.uri http://hdl.handle.net/1928/12630
dc.description.abstract Poor wound healing is a serious medical issue of particular concern in the elderly and people with diabetes. One major obstacle for these patients to achieve complete wound healing is incomplete reepithelialization which is necessary for restoration of barrier function. One molecule that has promising therapeutic value for promoting reepithelialization is epidermal growth factor receptor (EGFR). Using a squamous cell carcinoma cell line (SCC 12F) that expresses moderate levels of EGFR, we investigated the contributions of EGFR activation to reepithelialization, and specifically its roles in modulation of cell-cell junctions. Decreased cell-cell adhesion mediated by adherens junctions and desmosomes is necessary for epithelial outgrowth into the wound area. We find that elevated EGFR levels are necessary for successful reepithelialization in an in vitro model. EGFR activation led to junctional and cytoskeletal disruption, nuclear localization of the junctional protein ß-catenin and upregulation of target genes involved in wound healing. We also find desmosomes and adherens junctions are modulated by different mechanisms. EGF stimulation caused the desmosomal cadherin desmoglein-2 to internalize and enter a recycling pathway, while the adherens junction protein E-cadherin underwent a matrix metalloproteinase-dependent cleavage. We conclude that EGFR can stimulate multiple mechanisms within a given cell type leading to modulation of cadherin function, and that the stimulus is an important determinant in junctional protein fate. Understanding the mechanisms that promote reepithelialization may lead to strategies to improve wound repair in populations predisposed to poor wound healing. en_US
dc.language.iso en_US en_US
dc.subject keratinocytes en_US
dc.subject wound healing en_US
dc.subject.lcsh Keratinocytes.
dc.subject.lcsh Cell junctions.
dc.subject.lcsh Wound healing.
dc.subject.lcsh Epidermal growth factor--Receptors.
dc.title Dynamics of cell-cell junctions in keratinocytes en_US
dc.type Dissertation en_US
dc.description.degree Biomedical Sciences en_US
dc.description.level Doctoral en_US
dc.description.department University of New Mexico. Biomedical Sciences Graduate Program en_US
dc.description.advisor Hudson, Laurie
dc.description.committee-member Wandinger-Ness, Angela
dc.description.committee-member Orlando, Robert
dc.description.committee-member Felton, Linda


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