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

研究成果: 雜誌貢獻文章

3 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)910-920
頁數11
期刊Journal of Cellular and Molecular Medicine
24
發行號1
DOIs
出版狀態已發佈 - 一月 1 2020

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

指紋 深入研究「Inhibition of miR-21 alleviated cardiac perivascular fibrosis via repressing EndMT in T1DM」主題。共同形成了獨特的指紋。

  • 引用此

    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