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Dynamically Regulated CFTR Expression and Its Functional Role in Cutaneous Wound Healing

机译:动态调节雌性生殖道及其表达式在皮肤伤口愈合功能的作用

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The physiological role of cystic fibrosis transmembrane conductance regulator (CFTR) in keratinocytes and skin wound healing is completely unknown. The present study shows that CFTR is expressed in the multiple layers of keratinocytes in mouse epidermis and exhibits a dynamic expression pattern in a dorsal skin wound healing model, with diminishing levels observed from day 3 to day 5 and re-appearing from day 7 to day 10 after wounding. Knockdown of CFTR in cultured human keratinocytes promotes cell migration but inhibits differentiation, while overexpression of CFTR suppresses migration but enhances differentiation, indicating an important role of CFTR in regulating keratinocyte behavior. In addition, we have demonstrated a direct association of CFTR with epithelial junction formation as knockdown of CFTR downregulates the expression of adhesion molecules, such as E-cadherin, ZO-1 and -catenin, and disrupts the formation of cell junction, while overexpression of CFTR enhances cell junction formation. More importantly, we have shown that F508cftr-/- mice with defective CFTR exhibit delayed wound healing as compared to wild type mice, indicating that normal function of CFTR is critical for wound repair. Taken together, the present study has revealed a previously undefined role of CFTR in regulating skin wound healing processes, which may have implications in injury repair of other epithelial tissues. J. Cell. Physiol. 230: 2049-2058, 2015. (c) 2015 Wiley Periodicals, Inc.
机译:囊性纤维化的生理作用跨膜电导监管机构(雌性生殖道)角化细胞和皮肤伤口愈合完全未知的。雌性生殖道表达多层次的表皮角化细胞在小鼠和展览动态表达式模式背皮肤伤口治疗模式,减少水平从第三天到第五天,一会儿从7天受伤后第十天。培养人角质细胞促进细胞迁移,但抑制分化,而过度的雌性生殖道抑制迁移提高分化,表明一个重要雌性生殖道的作用在调节角化细胞的行为。此外,我们演示了一个直接协会的雌性生殖道上皮交界处雌性生殖道的降价会使形成表达粘附分子,如钙粘蛋白,ZO-1连环蛋白,扰乱了细胞结的形成,而过度雌性生殖道增强细胞连接形成。重要的是,我们已经表明,F508cftr - / -小鼠与有缺陷的雌性生殖道展览延迟伤口愈合与野生型小鼠相比,表明CFTR正常功能的检测对伤口至关重要修复。揭示了雌性生殖道的先前定义的角色调节皮肤伤口愈合过程可能在损伤修复其他有影响吗上皮组织。2049 - 2058年,2015年。

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