Wang Xueling, Yan Xiaoting, Huang Fang, Wu Lijuan
School of Medicine, Taizhou University, No. 1139, Shifu Avenue, Taizhou, Zhejiang 318000, China.
Taizhou Central Hospital, Taizhou, 318000, China.
Open Life Sci. 2023 Aug 10;18(1):20220679. doi: 10.1515/biol-2022-0679. eCollection 2023.
The aim of this study was to investigate the effects of adiponectin (APN) on the proliferation and phenotypic transformation of human skin fibroblasts (HSFs) induced by TGF-β1. Primary fibroblast cultures were collected from prepuce surgery, and the cell viability and proliferative activity of HSFs were detected by Cell Counting Kit-8 and EdU assays. In addition, cell migration was detected by Transwell assay. The protein levels of related genes in HSF were detected by Western blotting. The results showed that the proliferation and migration abilities of HSF in the TGF-β1 group were significantly improved, and the relative protein expression levels of PCNA, α-SMA, and Collagen I in the TGF-β1 group were greatly increased. Furthermore, TGF-β1 stimulated the phosphorylation of p38 in HSF, while APN pretreatment significantly inhibited the TGF-β1-induced phosphorylation of p38. Additionally, blocking the p38 MAPK signaling pathway relieved the injury in the HSF induced by TGF-β1 and enhanced the therapeutic effect of APN in the TGF-β1-treated HSF. In conclusion, APN inhibits TGF-β1-induced HSF proliferation and myofibroblast phenotypic transformation by activating the p38 MAPK signaling pathway. APN is expected to become a potential target for preventing and treating skin fibrosis and pathological scars.
本研究旨在探讨脂联素(APN)对转化生长因子-β1(TGF-β1)诱导的人皮肤成纤维细胞(HSFs)增殖及表型转化的影响。从包皮环切手术中收集原代成纤维细胞培养物,采用细胞计数试剂盒-8(Cell Counting Kit-8)和EdU检测法检测HSFs的细胞活力和增殖活性。此外,采用Transwell检测法检测细胞迁移情况。通过蛋白质免疫印迹法检测HSF中相关基因的蛋白水平。结果显示,TGF-β1组HSFs的增殖和迁移能力显著提高,TGF-β1组中增殖细胞核抗原(PCNA)、α-平滑肌肌动蛋白(α-SMA)和Ⅰ型胶原蛋白的相对蛋白表达水平大幅升高。此外,TGF-β1刺激HSF中p38的磷酸化,而APN预处理显著抑制TGF-β1诱导的p38磷酸化。另外,阻断p38丝裂原活化蛋白激酶(MAPK)信号通路可减轻TGF-β1诱导的HSF损伤,并增强APN对TGF-β1处理的HSF的治疗效果。综上所述,APN通过激活p38 MAPK信号通路抑制TGF-β1诱导的HSF增殖和肌成纤维细胞表型转化。APN有望成为预防和治疗皮肤纤维化及病理性瘢痕的潜在靶点。