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.
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.
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缺氧会抑制人类皮肤模型中的基底角质形成细胞增殖，并诱导表皮粘附连接蛋白、水通道蛋白-3 和糖原分布的区域特异性变化。
DOI：
10.1111/j.1524-475x.2009.00515.x
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Allen-Hoffmann,BLynn
中科院分区：
文献类型：
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作者：
Straseski,JoelyA;Gibson,AngelaL;Thomas-Virnig,ChristinaL;Allen-Hoffmann,BLynn
人们普遍认为，缺氧和从缺氧中恢复有助于人类皮肤的破裂和溃疡。首次在人体皮肤器官型模型中研究了这些应力对细胞增殖、分化和细胞间粘附分子表达的影响。完全分层的组织暴露于缺氧和随后的复氧的时间过程。观察到角质形成细胞形态、糖原储存和细胞连接的区域变化，表皮的更多分化层表现出缺氧的第一个证据。颗粒层内的细胞肿胀与水通道蛋白-3消耗同时发生。缺氧后，角质形成细胞粘附连接蛋白E-钙粘蛋白和β-连环蛋白在整个表皮中以区域特异性方式显著降低。相比之下，P-钙粘蛋白和桥粒蛋白桥粒斑蛋白和桥粒芯糖蛋白-1对缺氧不敏感。相对于常氧对照，缺氧组织表现出增加的转录抑制物鼻涕虫的mRNA水平，然而，相关的转录因子蜗牛的mRNA水平不受影响。所有的细胞和分子变化是可逆的复氧。这些结果表明，缺氧和复氧对表皮粘附蛋白产生不同的影响，并表明钙粘蛋白、β-连环蛋白和Slug在复层鳞状上皮缺氧诱导的连接变化中发挥新的作用。
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.