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Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
MicroRNA-19 upregulation attenuates cardiac fibrosis via targeting connective tissue growth factor
Xiaozheng Song1, Yuqiang Cui1, Teng Zhu1
1Department of Cardiology, Shengli Oilfield Central Hospital, 31 Jinan Road, Dongying 257034, China.
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.
Insights
Upregulating microRNA-19 (miR-19) improves heart function and reduces cardiac fibrosis. This occurs by inhibiting connective tissue growth factor (CTGF) and mitogen-activated protein kinase (MAPK) pathways, offering a potential therapeutic strategy.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Fibrosis Research
Background:
- MicroRNA-19 (miR-19) has been implicated in aging-related heart failure.
- Cardiac fibrosis is a key pathological feature contributing to heart dysfunction.
Purpose of the Study:
- To investigate the role of miR-19 in cardiac fibrosis.
- To identify the molecular targets of miR-19 in the context of fibrosis.
Main Methods:
- Cardiac fibrosis was induced in rats via myocardial infarction (MI) and in cardiac fibroblasts (CFs) using angiotensin II (Ang II).
- miR-19 expression levels were measured, and the effects of miR-19 administration were assessed.
- Bioinformatic analysis and luciferase reporter assays were used to identify miR-19 targets.
- Western blotting was used to analyze protein expression, including CTGF and MAPK pathway components.
Main Results:
- miR-19 expression was decreased in fibrotic heart tissue and Ang II-treated CFs.
- miR-19 administration improved cardiac function and reversed fibrosis markers (collagen I, collagen III, TGF-β).
- Connective tissue growth factor (CTGF) was confirmed as a direct miR-19 target, and miR-19 inhibited CTGF and MAPK signaling (ERK, JNK, p38).
Conclusions:
- Upregulating miR-19 can improve cardiac function and attenuate cardiac fibrosis.
- Inhibition of CTGF and MAPK pathways by miR-19 is a key mechanism underlying its cardioprotective effects.
