Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity.

Abstract

Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro. Moreover, it prevented interstitial collagen deposition and expression of fibrosis-associated genes. Upregulation of collagen type I by Smad3 overexpression was observed in cardiac myoblast H9c2 cells but not in cardiac fibroblasts. Gallic acid reduced the DNA binding activity of phosphorylated Smad3 in Smad binding sites of collagen type I promoter in rat cardiac fibroblasts. Furthermore, it decreased the ISP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) protein in mice. JNK2 overexpression reduced collagen type I and Smad3 expression as well as GATA4 expression in H9c2 cells and cardiac fibroblasts. Gallic acid might be a novel therapeutic agent for the prevention of cardiac hypertrophy and fibrosis by regulating the JNK2 and Smad3 signaling pathway.

• Authors: Yuhee Ryu, Li Jin, Hae Jin Kee, Zhe Hao Piao, Jae Yeong Cho, Gwi Ran Kim, Sin Young Choi, Ming Quan Lin, Myung Ho Jeong
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 34790 (10 05 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27703224 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Smad3 Protein
• Smad3 protein, mouse
• Gallic Acid
• Mitogen-Activated Protein Kinase 9
• Isoproterenol

Topics

• Animals
• Cardiomegaly (chemically induced, metabolism, physiopathology, prevention & control)
• Cells, Cultured
• Disease Models, Animal
• Fibrosis
• Gallic Acid (administration & dosage, pharmacology)
• Gene Expression Regulation (drug effects)
• Heart Ventricles (drug effects, physiopathology)
• Isoproterenol (adverse effects)
• Male
• Mice
• Mitogen-Activated Protein Kinase 9 (genetics, metabolism)
• Protein Binding
• Signal Transduction (drug effects)
• Smad3 Protein (genetics, metabolism)
• Ventricular Function, Left (drug effects)