Fibroblasts (FBs) are the most important functional cells in the process of wound repair, and their functions can be activated by different signals at the pathological site. Although wound repair is associated with microenvironmental stiffness, the effect of matrix stiffness on FBs remains elusive. In this study, TGF-β1 was used to mimic the fibrotic environment under pathological conditions. We found that the soft substrates made FBs slender compared with tissue culture plastic, and the main altered biological function was the inhibition of proliferation and differentiation ability. Through PPI and WGCNA analysis, 63 hub genes were found, including GADD45A, CDKN3, HIST2H3PS2, ACTB, etc., which may be the main targets of soft substrates affecting the proliferation and differentiation of FBs. Our findings not only provide a more detailed report on the effect of matrix stiffness on the function of human skin FBs, but also may provide new intervention ideas for improving scars and other diseases caused by excessive cell proliferation, with potential clinical application prospects.

中文翻译：

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集成 PPI 和 WGCNA 检索中枢基因特征，用于抑制人成纤维细胞增殖和分化的软底物

成纤维细胞（FBs）是伤口修复过程中最重要的功能细胞，其功能可被病理部位的不同信号激活。尽管伤口修复与微环境刚度有关，但基质刚度对 FB 的影响仍然难以捉摸。在这项研究中，TGF-β1 被用来模拟病理条件下的纤维化环境。我们发现，与组织培养塑料相比，软基质使FBs变细，主要改变的生物学功能是抑制增殖和分化能力。通过PPI和WGCNA分析，发现63个hub基因，包括GADD45A、CDKN3、HIST2H3PS2、ACTB等，可能是软底物影响FBs增殖分化的主要靶点。