Abstract
Background
Previous studies have shown the role of microRNA (miR)-19 in aging-related heart failure.
The present study aimed to verify the effects of miR-19 on cardiac fibrosis and its
target.
Methods
Cardiac fibrosis was induced by myocardial infarction (MI)-induced heart failure and
angiotensin (Ang) II-treated rats in vivo, and was induced in Ang II-treated cardiac fibroblasts (CFs) in vitro.
Results
The expression of miR-19 was reduced in the heart tissue of MI and Ang II-treated
rats, and Ang II-treated CFs. The impaired cardiac function in rats was repaired after
miR-19 administration. The levels of collagen I, collagen III and transforming growth
factor-beta (TGF-β) increased in the heart tissue of MI and Ang II-treated rats, and
Ang II-treated CFs. These increases were reversed by miR-19 agomiR. Moreover, the
bioinformatic analysis and luciferase reporter assays demonstrated that connective
tissue growth factor (CTGF) was a direct target of miR-19. MiR-19 treatment inhibited
CTGF expression in CFs, while CTGF overexpression inhibited miR-19 agomiR to attenuate
the Ang II-induced increases of collagen I and collagen III in CFs. The increases
of p-ERK, p-JNK and p-p38 in the CFs induced by Ang II were repressed by miR-19 agomiR.
Conclusions
Upregulating miR-19 can improve cardiac function and attenuate cardiac fibrosis by
inhibiting the CTGF and MAPK pathways.
Key Indexing Terms
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Article info
Publication history
Published online: December 16, 2022
Accepted:
December 13,
2022
Received:
October 1,
2021
Identification
Copyright
© 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
