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Oxygen deprivation inhibits basal keratinocyte proliferation in a model of human skin and induces regio‐specific changes in the distribution of epidermal adherens junction proteins, aquaporin‐3, and glycogen
Author(s) -
Straseski Joely A.,
Gibson Angela L.,
ThomasVirnig Christina L.,
AllenHoffmann B. Lynn
Publication year - 2009
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2009.00515.x
Subject(s) - adherens junction , microbiology and biotechnology , keratinocyte , biology , epidermis (zoology) , cadherin , glycogen , lamellar granule , chemistry , cell , endocrinology , biochemistry , anatomy , in vitro , ultrastructure
It is generally accepted that hypoxia and recovery from oxygen deprivation contribute to the breakdown and ulceration of human skin. The effects of these stresses on proliferation, differentiation and expression of cell–cell adhesion molecules were investigated for the first time in an organotypic model of human skin. Fully stratified tissues were exposed to a time course of oxygen deprivation and subsequent reoxygenation. Regional changes in keratinocyte morphology, glycogen stores and cellular junctions were observed, with more differentiated layers of the epidermis exhibiting the first evidence of oxygen deprivation. Cellular swelling within the granular layer was concurrent with aquaporin‐3 depletion. The keratinocyte adherens junction proteins E‐cadherin and β‐catenin were dramatically decreased in a regio‐specific manner throughout the epidermis following oxygen deprivation. In contrast, P‐cadherin and the desmosomal proteins desmoplakin and desmoglein‐1 were refractory to oxygen deprivation. Relative to normoxic controls, hypoxic tissues exhibited increased mRNA levels of the transcriptional repressor Slug; however, mRNA levels of the related transcriptional factor Snail were unaffected. All cellular and molecular changes were reversible upon reoxygenation. These results show that oxygen deprivation and reoxygenation exert differential effects on epidermal adhesion proteins and suggest a novel role for cadherins, β‐catenin, and Slug in hypoxia‐induced junctional changes occurring in stratified squamous epithelium.