KLF13 promotes VSMCs phenotypic dedifferentiation by directly binding to the SM22α promoter

作者全名：Yuan, Xiaofan; Jiang, Chuan; Xue, Yuzhou; Guo, Fuqiang; Luo, Minghao; Guo, Lei; Gao, Yang; Yuan, Tongling; Xu, Hui; Chen, Hong

作者地址：[Yuan, Xiaofan; Gao, Yang; Yuan, Tongling; Xu, Hui; Chen, Hong] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Sch Med, Dept Gen Practice, Chengdu, Sichuan, Peoples R China; [Jiang, Chuan] Southwest Med Univ, Dept Neurosurg, Luzhou, Sichuan, Peoples R China; [Xue, Yuzhou] Peking Univ Third Hosp, Dept Cardiol, Beijing, Peoples R China; [Guo, Fuqiang; Guo, Lei] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Sch Med, Dept Neurol, Chengdu, Sichuan, Peoples R China; [Luo, Minghao] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Chongqing, Peoples R China; [Chen, Hong] 32 West second Sect,1st Ring Rd, Chengdu, Peoples R China

通信作者：Chen, H (通讯作者)，32 West second Sect,1st Ring Rd, Chengdu, Peoples R China.

来源：JOURNAL OF CELLULAR PHYSIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001204945100001

JCR分区：Q1

影响因子：4.5

年份：2024

卷号：239

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：atherosclerosis; dedifferentiation; Kruppel-like factor 13; re-stenosis; SM22 alpha; vascular smooth muscle cells

摘要：Kruppel-like factor 13 (KLF13), a zinc finger transcription factor, is considered as a potential regulator of cardiomyocyte differentiation and proliferation during heart morphogenesis. However, its precise role in the dedifferentiation of vascular smooth muscle cells (VSMCs) during atherosclerosis and neointimal formation after injury remains poorly understood. In this study, we investigated the relationship between KLF13 and SM22 alpha expression in normal and atherosclerotic plaques by bioanalysis, and observed a significant increase in KLF13 levels in the atherosclerotic plaques of both human patients and ApoE-/- mice. Knockdown of KLF13 was found to ameliorate intimal hyperplasia following carotid artery injury. Furthermore, we discovered that KLF13 directly binds to the SM22 alpha promoter, leading to the phenotypic dedifferentiation of VSMCs. Remarkably, we observed a significant inhibition of platelet-derived growth factor BB-induced VSMCs dedifferentiation, proliferation, and migration when knocked down KLF13 in VSMCs. This inhibitory effect of KLF13 knockdown on VCMC function was, at least in part, mediated by the inactivation of p-AKT signaling in VSMCs. Overall, our findings shed light on a potential therapeutic target for treating atherosclerotic lesions and restenosis after vascular injury.

基金机构：Key Research and Development Program of Sichuan Province; Natural Science Foundation of Sichuan Province [24NSFSC2240]; [2022YFS0264]; [2023YFS0274]

基金资助正文：The authors gratefully acknowledge the patients participated in this study. This study is supported by the Natural Science Foundation of Sichuan Province (24NSFSC2240), the Key Research and Development Program of Sichuan Province (2022YFS0264 and 2023YFS0274).