GATA6 triggers fibroblast activation and tracheal fibrosis through the Wnt/beta-catenin pathway

作者全名："Li, Anmao; Gu, Lei; Li, Junhao Mu Yishi; Wang, Xiaohui; Jiang, Jinyue; Bai, Yang; Yang, Mingjin; He, Chunyan; Xiao, Rui; Liao, Jiaxin; Jin, Xingxing; Xiao, Meiling; Xiao, Yang; Zhang, Xia; Tan, Tairong; Peng, Mingyu; Xu, Li; Guo, Shuliang"

作者地址："[Li, Anmao; Gu, Lei; Li, Junhao Mu Yishi; Wang, Xiaohui; Jiang, Jinyue; Bai, Yang; Yang, Mingjin; He, Chunyan; Xiao, Rui; Liao, Jiaxin; Jin, Xingxing; Xiao, Meiling; Xiao, Yang; Zhang, Xia; Tan, Tairong; Peng, Mingyu; Xu, Li; Guo, Shuliang] Chongqing Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 1, Chongqing, Peoples R China; [Xu, Li; Guo, Shuliang] Chongqing Med Univ, Dept Pulm & Crit Care Med, Affiliated Hosp 1, Chongqing, Peoples R China"

通信作者："Xu, L; Guo, SL (通讯作者)，Chongqing Med Univ, Dept Pulm & Crit Care Med, Affiliated Hosp 1, Chongqing, Peoples R China."

来源：CELLULAR SIGNALLING

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000931534500001

JCR分区：Q2

影响因子：4.4

年份：2023

卷号：105

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Tracheal fibrosis; Fibroblast activation; GATA6; Wnt; -catenin signaling

摘要："Tracheal fibrosis is a key abnormal repair process leading to fatal stenosis, characterized by excessive fibroblast activation and extracellular matrix (ECM) deposition. GATA6, a zinc finger-containing transcription factor, is involved in fibroblast activation, while its role in tracheal fibrosis remains obscure. The present study investi-gated the potential role of GATA6 as a novel regulator of tracheal fibrosis. It was found that GATA6 and alpha-smooth muscle actin (alpha-SMA) were obviously increased in tracheal fibrotic granulations and in TGF beta 1-treated primary tracheal fibroblasts. GATA6 silencing inhibited TGF beta 1-stimulated fibroblast proliferation and ECM synthesis, promoted cell apoptosis, and inactivated Wnt/beta-catenin pathway, whereas GATA6 overexpression showed the reverse effects. SKL2001, an agonist of Wnt/beta-catenin signaling, restored collagen1a1 and alpha-SMA expression which was suppressed by GATA6 silencing. Furthermore, in vivo, knockdown of GATA6 ameliorated tracheal fibrosis, as manifested by reduced tracheal stenosis and ECM deposition. GATA6 inhibition in rat tracheas also impaired granulation proliferation, increased apoptosis, and inactivated Wnt/beta-catenin pathway. In conclusion, our findings indicate that GATA6 triggers fibroblast activation, cell proliferation, and apoptosis resistance in tracheal fibrosis via the Wnt/beta-catenin signaling pathway. Targeting GATA6 may represent a promising thera-peutic approach for tracheal fibrosis."

基金机构：Experimental Research Center of the first affiliated hospital of Chongqing medical university

基金资助正文：We would like to thank the Experimental Research Center of the first affiliated hospital of Chongqing medical university for providing experimental site support.