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Updated: Aug 15, 2026
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
MicroRNA-34a regulates cardiac fibrosis after myocardial infarction by targeting Smad4
Ying Huang1, Yuan Qi, Jian-Qing Du
1Pu Dong New Area People's Hospital, Department of Cardiology , Huan-Nan Road 490#, Shanghai, 201200 , China +86 021 50331692 ; +86 021 50331692 ; daifu_zhang001@163.com.
Background:
Although few microRNAs (miRNAs) have been involved in the regulation of post-ischemic cardiac fibrosis, the exact effect and underlying mechanism of miRNAs in cardiac fibrosis remains unclear. Here, we sought to investigate whether microRNA-34 (miR-34) plays a role in the pathogenic development of myocardial fibrosis.
Methods:
The myocardial infarction (MI) mice model was induced and cardiac fibroblasts were cultured. Histological analyses, quantitative real-time polymerase chain reaction and Western blotting analysis were used.
Results:
We found that the miR-34 cluster, especially miR-34a, was upregulated in the MI heart. In vivo, inhibition of miR-34a reduces the severity of experimental cardiac fibrosis in mice. TGF-β1 increased miR-34a expression in cardiac fibroblasts. Overexpressing miR-34a levels increased the profibrogenic activity of TGF-β1 in cardiac fibroblast, whereas inhibition miR-34a levels weakened the activity. Finally, we showed that miR-34a's underlying mechanism during cardiac fibrosis occurs through the targeting of Smad4 expression.
Conclusions:
Our findings provide evidence that miR-34a plays a critical role in the progression of cardiac tissue fibrosis by directly targeting Smad4, which suggests that miR-34a may be new marker for cardiac fibrosis progression and that inhibition of miR-34a may be a promising strategy in the treatment of cardiac fibrosis.
Insights
MicroRNA-34a (miR-34a) is upregulated after myocardial infarction and promotes cardiac fibrosis by targeting Smad4. Inhibiting miR-34a may be a promising therapeutic strategy for cardiac fibrosis.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Fibrosis Research
Background:
- MicroRNAs (miRNAs) role in post-ischemic cardiac fibrosis is not fully understood.
- Investigating the specific function of microRNA-34 (miR-34) in myocardial fibrosis pathogenesis.
Purpose of the Study:
- To determine if miR-34 plays a role in myocardial fibrosis.
- To elucidate the mechanism by which miR-34a influences cardiac fibrosis progression.
Main Methods:
- Myocardial infarction (MI) mouse model induction and cardiac fibroblast culture.
- Histological analysis, quantitative real-time polymerase chain reaction, and Western blotting.
- In vivo and in vitro experiments to assess miR-34a function and regulation.
Main Results:
- miR-34a was significantly upregulated in MI hearts.
- Inhibition of miR-34a reduced cardiac fibrosis severity in mice.
- Transforming growth factor-beta 1 (TGF-β1) increased miR-34a expression; miR-34a enhanced TGF-β1 profibrotic activity.
- miR-34a targets Smad4 expression to mediate cardiac fibrosis.
Conclusions:
- miR-34a is critical in cardiac fibrosis progression by targeting Smad4.
- miR-34a may serve as a biomarker for cardiac fibrosis.
- Inhibiting miR-34a presents a potential therapeutic approach for cardiac fibrosis.
