Lin Guangmin, Cao Ning, Wu Jinhong, Zheng Meilian, Yang Zhaobin
Department of Plastic and Cosmetic Surgery, Zhangzhou Hospital Affiliated of Fujian Medical University, Zhangzhou Municipal Hospital of Fujian Province, No. 59, Shengli West Road, Xiangcheng District, Zhangzhou City, 363000, Fujian Province, China.
Medical Intensive Care Unit, Zhangzhou Hospital Affiliated of Fujian Medical University, Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou City, Fujian Province, China.
Arch Dermatol Res. 2025 Jan 9;317(1):214. doi: 10.1007/s00403-024-03692-9.
The fibrosis of pathologic scar (PS) is formed by the excessive deposition of extracellular matrix, resulting in an abnormal scar. Recent clinical tests have indicated that the regulation of PS fibroblast cells (PSF cells) proliferation can serve as an intervention measure for PS. Our work aimed to elucidate the specific mechanism of action of TCF4 on the progression of PS fibrosis.
Our study used qRT-PCR and Western blot to search for the expression of key proteins in PS clinical samples and cells. Transwell, CCK-8, and wound scratch assays were employed to analyze the proliferation and migration of PSF cells. CHIP, dual-luciferase reporter experiments, and bio-informatics analysis were used to analyze the interactions between molecules.
The analysis of PS clinical samples confirmed a positive correlation between TCF4 and miR-494-3p. This regulatory mechanism was related to the progression of PS. We verified that the overexpression of miR-494-3p or the knockdown of THBS1 both suppressed the proliferation and migration of PSF cells. Furthermore, we also confirmed the binding relationships between TCF4, miR-494-3p, and THBS1. Simultaneously, we verified the existence of the TCF4/miR-494-3p/THBS1 regulatory network in PS. This regulatory process affects the development of PS fibrosis.
Our study results indicate that TCF4, miR-494-3p, and THBS1 are abnormally expressed in PS. TCF4 increases the proliferation and migration ability of PSF cells through the miR-494-3p/THBS1 signaling pathway, which promotes the fibrosis of PS.
病理性瘢痕（PS）的纤维化是由细胞外基质过度沉积形成的，导致瘢痕异常。近期临床试验表明，调控PS成纤维细胞（PSF细胞）增殖可作为PS的一种干预措施。我们的研究旨在阐明TCF4在PS纤维化进展中的具体作用机制。
我们的研究采用qRT-PCR和蛋白质免疫印迹法来检测PS临床样本和细胞中关键蛋白的表达。运用Transwell实验、CCK-8实验和划痕实验分析PSF细胞的增殖和迁移能力。采用染色质免疫沉淀技术（CHIP）、双荧光素酶报告基因实验和生物信息学分析来分析分子间的相互作用。
对PS临床样本的分析证实TCF4与miR-494-3p呈正相关。这种调控机制与PS的进展有关。我们证实，miR-494-3p的过表达或THBS1的敲低均抑制了PSF细胞的增殖和迁移。此外，我们还证实了TCF4、miR-494-3p和THBS1之间的结合关系。同时，我们验证了PS中存在TCF4/miR-494-3p/THBS1调控网络。这一调控过程影响PS纤维化的发展。
我们的研究结果表明，TCF4、miR-494-3p和THBS1在PS中异常表达。TCF4通过miR-494-3p/THBS1信号通路增强PSF细胞的增殖和迁移能力，从而促进PS的纤维化。
