AUTHOR=Liao Rongheng , Qi Zhen , Tang Ri , Wang Renrong , Wang Yongyi 

TITLE=Methyl Ferulic Acid Attenuates Human Cardiac Fibroblasts Differentiation and Myocardial Fibrosis by Suppressing pRB-E2F1/CCNE2 and RhoA/ROCK2 Pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.714390

DOI=10.3389/fphar.2021.714390

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Myocardial fibrosis is a key pathological process after myocardial infarction, which leads to poor outcomes in patients at the end stage. Effective treatments for improving prognosis of myocardial fibrosis are needed to be further developed. Methyl ferulic acid (MFA), a biologically active monomer extracted and purified from the Chinese herbal medicine, is reported as an attenuator in many diseases. In this study, we aim to reveal the role it plays in myocardial fibrosis after myocardial infarction and its possible mechanism.</p><p><bold>Results:</bold> Firstly, we found that MFA attenuated the expression of fibrosis-related proteins and the ability of migration and proliferation in TGF-β1–induced human cardiac fibroblasts (HCFs). Then, myocardial fibrosis after myocardial infarction models on mouse was built to reveal the <italic>in vivo</italic> affection of MFA. After 28 days of treatments, fibrosis areas, cardiac function, and expression of fibrosis-related proteins were all improved in the MFA-treated group than the myocardial infarction group. Finally, to elucidate the mechanism of phenomenon we observed, we found that MFA attenuated HCF differentiation after myocardial infarction by suppressing the migration and proliferation in HCFs, which was by suppressing the pRB-E2F1/CCNE2 and the RhoA/ROCK2 pathway.</p><p><bold>Conclusion:</bold> Our findings showed that MFA attenuated the expression of fibrosis-related proteins, and the ability of migration and proliferation in HCFs improved the cardiac function of myocardial infarction mice; meanwhile, the mechanism of that was by suppressing the pRB-E2F1/CCNE2 and the RhoA/ROCK2 pathway.</p>