Inhibition of miR-21 alleviated cardiac perivascular fibrosis via repressing EndMT in T1DM

Qianqian Li, Yufeng Yao, Shumei Shi, Mengchen Zhou, Yingchao Zhou, Mengru Wang, Jeng Jiann Chiu, Zhengrong Huang, Weili Zhang, Min Liu, Qing Wang, Xin Tu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In type 1 and type 2 diabetes mellitus, increased cardiac fibrosis, stiffness and associated diastolic dysfunction may be the earliest pathological phenomena in diabetic cardiomyopathy. Endothelial-mesenchymal transition (EndMT) in endothelia cells (ECs) is a critical cellular phenomenon that increases cardiac fibroblasts (CFs) and cardiac fibrosis in diabetic hearts. The purpose of this paper is to explore the molecular mechanism of miR-21 regulating EndMT and cardiac perivascular fibrosis in diabetic cardiomyopathy. In vivo, hyperglycaemia up-regulated the mRNA level of miR-21, aggravated cardiac dysfunction and collagen deposition. The condition was recovered by inhibition of miR-21 following with improving cardiac function and decreasing collagen deposition. miR-21 inhibition decreased cardiac perivascular fibrosis by suppressing EndMT and up-regulating SMAD7 whereas activating p-SMAD2 and p-SMAD3. In vitro, high glucose (HG) up-regulated miR-21 and induced EndMT in ECs, which was decreased by inhibition of miR-21. A highly conserved binding site of NF-κB located in miR-21 5′-UTR was identified. In ECs, SMAD7 is directly regulated by miR-21. In conclusion, the pathway of NF-κB/miR-21/SMAD7 regulated the process of EndMT in T1DM, in diabetic cardiomyopathy, which may be regarded as a potential clinical therapeutic target for cardiac perivascular fibrosis.

Original languageEnglish
Pages (from-to)910-920
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

Keywords

  • cardiac perivascular fibrosis
  • diabetic cardiomyopathy
  • endothelial-mesenchymal transition
  • microRNA
  • SMAD7

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Fingerprint Dive into the research topics of 'Inhibition of miR-21 alleviated cardiac perivascular fibrosis via repressing EndMT in T1DM'. Together they form a unique fingerprint.

  • Cite this

    Li, Q., Yao, Y., Shi, S., Zhou, M., Zhou, Y., Wang, M., Chiu, J. J., Huang, Z., Zhang, W., Liu, M., Wang, Q., & Tu, X. (2020). Inhibition of miR-21 alleviated cardiac perivascular fibrosis via repressing EndMT in T1DM. Journal of Cellular and Molecular Medicine, 24(1), 910-920. https://doi.org/10.1111/jcmm.14800