Rationale: Mechanical stimuli in the microenvironment are considered key regulators of cell function. Clinically, mechanical force (tissue expander) is widely used to regenerate skin for post-burn or trauma repair, implying that mechanical stretching can promote skin cell regeneration and proliferation. However, the underlying mechanism remains unknown./nMethods: Microarray analysis was utilized to detect the hub gene. The expression of Cdh1 as examined in cells and tissues by western blot, q-PCR and immunohistochemistry staining respectively. Biological roles of Cdh1 was revealed by a series of functional in vitro and in vivo studies./nResults: Microarray analysis identified Cdh1 as a hub gene related to skin regeneration during rat cutaneous mechanical loading. In vitro studies suggested that both mechanical loading and Cdh1 interference induced keratinocyte dedifferentiation and enhanced stemness, promoting cell proliferation and prevent apoptosis. Furthermore, the forkhead box O1/Krüppel-like factor 4 (FOXO1/KLF4) pathway was activated and contributed to the keratinocyte dedifferentiation. In vivo studies showed that mechanical loading and Cdh1 interference facilitated epidermal dedifferentiation and promoted dermal collagen deposition, and that Cdh1 overexpression could block such influence./nConclusions: In this study, we show that E-cadherin (CDH1), a well-known cell-cell adhesion molecule, plays a crucial role in mechanical stretch-induced skin cell regeneration and proliferation. We have shown for the first time the process by which mechanical stress is transmitted to the epidermis and induces a downstream signaling pathway to induce epidermal cells to differentiate. These findings demonstrate that Cdh1-induced keratinocyte dedifferentiation is a crucial event in mechanical stretch-mediated skin regeneration and that Cdh1 may serve as a potential therapeutic target for promoting skin regeneration.

中文翻译：

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CDH1 被确定为机械负荷后皮肤再生的治疗靶点


理由：微环境中的机械刺激被认为是细胞功能的关键调节因素。临床上，机械力（组织扩张器）广泛用于烧伤后或创伤修复的皮肤再生，这意味着机械拉伸可以促进皮肤细胞再生和增殖。然而，潜在的机制仍然未知。/n方法：利用微阵列分析来检测 hub 基因。分别通过蛋白质印迹、q-PCR和免疫组织化学染色检查细胞和组织中Cdh1的表达。一系列功能性体外和体内研究揭示了 Cdh1 的生物学作用。/n 结果：微阵列分析确定Cdh1是与大鼠皮肤机械负荷期间皮肤再生相关的枢纽基因。体外研究表明机械负荷和Cdh1干扰均可诱导角质形成细胞去分化并增强干性，促进细胞增殖并防止细胞凋亡。此外，叉头盒 O1/Krüppel 样因子 4 (FOXO1/KLF4) 通路被激活并促进角质形成细胞去分化。体内研究表明，机械负荷和Cdh1干扰促进表皮去分化并促进真皮胶原沉积，而Cdh1过表达可以阻止这种影响。/n 结论：在这项研究中，我们表明 E-钙粘蛋白 (CDH1)，一种众所周知的细胞间粘附分子在机械拉伸诱导的皮肤细胞再生和增殖中起着至关重要的作用。 我们首次展示了机械应力传递到表皮并诱导下游信号通路诱导表皮细胞分化的过程。这些发现表明， Cdh1诱导的角质形成细胞去分化是机械拉伸介导的皮肤再生中的关键事件，并且Cdh1可以作为促进皮肤再生的潜在治疗靶点。