The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
The First Norman Bethune Clinical Medical College, Jilin University, Changchun 130021, China.
Aging (Albany NY). 2022 Sep 2;14(17):6957-6974. doi: 10.18632/aging.204258.
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.
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硬度有关，但基质硬度对 FBs 的影响仍不清楚。在本研究中，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 变得更加细长，其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，发现了 63 个枢纽基因，包括 GADD45A、CDKN3、HIST2H3PS2、ACTB 等，它们可能是软基质影响 FBs 增殖和分化的主要靶点。我们的研究结果不仅提供了关于基质硬度对人皮肤 FBs 功能影响的更详细报告，而且可能为改善因细胞过度增殖而导致的疤痕等疾病提供新的干预思路，具有潜在的临床应用前景。
