miR-19a-3p enhances TGF-β1-induced cardiac fibroblast activation via targeting BAMBI
Pengxi Shi1
Ao Tan1
Yuanyuan Ma1
Lingli Que1
Chuanfu Li2
Yongfeng Shao3
Haoliang Sun3
Yuehua Li1
Jiantao Li1
1.Key Laboratory of Targeted Intervention of Cardiovascular Disease,Collaborative Innovation Center for Cardiovascular Disease Translational Medicine,School of Basic Medical Science,Nanjing Medical University,Nanjing,Jiangsu 211166,China2.Department of Surgery,East Tennessee State University,Johnson City,TN 37614-0575,USA3.Department of Cardiovascular Surgery,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210029,China
摘要：Myocardial fibrosis is a major pathogenic factor contributing to cardiac remodeling and heart failure.Recent research has indicated that microRNAs play a crucial role in the progression of cardiac fibrosis.Bone morphogenetic protein and activin membrane-bound inhibitor(BAMBI)have been shown to alleviate myocardial fibrosis by inhibiting the transforming growth factor β1(TGF-β1)signaling pathway.Therefore,the current study aimed to elucidate the post-transcriptional regulation of BAMBI by miR-19a-3p and its role in TGF-β1-induced cardiac fibroblast activation.We found that transverse aortic constriction induced both myocardial interstitial and perivascular collagen deposition.Quantitative reverse transcription-PCR(qRT-PCR)analysis showed that the expression level of miR-19a-3p was increased in the myocardial tissues of cardiac fibrosis,and TGF-β1 induced an upregulation in miR-19a-3p expression in cardiac fibroblasts.The dual-luciferase reporter assay and qRT-PCR verified that miR-19a-3p directly bound to the 3′ untranslated regions of BAMBI mRNA,thereby reducing BAMBI expression and diminishing its ability to inhibit the TGF-β1 signaling pathway.Furthermore,overexpression of miR-19a-3p mimic increased the activation of TGF-β1/SMAD2/3 pathway signaling,promoting cardiac fibroblast activation.However,this activation was blocked by BAMBI overexpression.These findings imply that miR-19a-3p enhances the activation of TGF-β1/SMAD2/3 by inhibiting BAMBI,further boosting the activation of cardiac fibroblasts and contributing to myocardial fibrosis.
机标关键词：fibroblastbambi1-inducedactivationcardiacenhancestargeting
分类号：R542.23(心脏、血管（循环系）疾病)
论文发表日期：2025-03-30
在线出版日期：2026-03-31（本平台首次上网日期，不代表文献的发表时间）
页数：14( 中插5,171-183 )
英文信息