Ellagic acid inhibits proliferation and migration of cardiac fibroblasts by down-regulating expression of HDAC1

Abstract

Cardiac fibroblasts (CFs) could be activated after myocardial infarction (MI). Thus, it is necessary to explore effective drugs to suppress the activation of CFs following MI. This study was designed to investigate the impacts of ellagic acid on CFs and the underlying mechanisms. The expression of histone deacetylases (HDACs) and fibrosis-related genes was detected by qRT-PCR and western blot. The Masson's Trichrome Staining assay was used to evaluate the area of cardiac fibrosis. The proliferation and migration of CFs were measured by CCK8 Kit and Transwell assay, respectively. Our results showed that ellagic acid significantly reduced protein expression of HDAC1, mRNA expression of collagen I, collagen III, MMP-2 and MMP-9 and the area of cardiac fibrosis in MI rats. In Ang II-stimulated CFs, ellagic acid (60 μmol/L) decreased the protein expression of HDAC1, collagen I, collagen III, MMP-2 and MMP-9, and inhibited cell proliferation and migration. Further, HDAC1 over-expression reversed the inhibitor effects of ellagic acid on proteins expression (collagen I, collagen III, MMP-2 and MMP-9) and proliferation and migration of CFs. The present results suggested that ellagic acid suppressed proliferation and migration of CFs by down-regulating expression of HDAC1.

Ellagic Acid Attenuates BLM-Induced Pulmonary Fibrosis via Inhibiting Wnt Signaling Pathway

“…Ellagic acid (EA) is generated by hydrolysis of complex polyphenolic compounds named ellagitannins, and found in a wide variety of fruits and nuts such black currants, grapes, raspberries and strawberries [21,22]. Ellagic acid has shown multiple protective effects during brotic diseases such as liver brosis, pancreatic brosis and cardiac brosis [23][24][25]. Ellagic acid promoted apoptosis and autophagy, suppressed Wnt/β-catenin and mTOR pathways in tumor cells [26][27][28].…”

HPLC‐QTOF/MS‐based metabolomics to explore the molecular mechanisms of Yiqi Fumai Lyophilized Injection in heart failure mice

“…Ketone bodies, the intermediates of valine, leucine, and isoleucine biosynthesis, including acetoacetate, 3‐hydroxybutyrate, and acetone, are used as an alternative fuel in CHF [38]. However, ketone bodies are much more than metabolites, for example, 3‐hydroxybutyrate was found to be the inhibitor of histone deacetylases (HDACs) and the downregulation of HDAC1 could inhibit the expression of proliferation and migration of MCFs [39]. It is also reported that trimetazidine decreased the levels of CVF and improved the cardiac functions accompanied by markedly enhanced ketone body metabolism expression in isoproterenol‐induced heart failure rats [40].…”

MiR-324-3p Regulates Fibroblast Proliferation via Targeting TGF-β1 in Atrial Fibrillation

“…A large number of studies have proved that myocardial fibroblast proliferation and migration are the essential features of myocardial fibrosis. 14,30,31) Therefore, we isolated the cardiac fibroblasts to explore the effect of miR-324-3p in myocardial fibrosis from the atrial tissue of AF rats. A previous study has shown that miR-324-3p suppresses nasopharyngeal carcinoma cell migration and invasion by targeting WNT2B.…”