title: 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.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju 501-757, Republic of Korea.
authors.forename: Yuhee
authors.initials: Y
authors.lastname: Ryu
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju 501-757, Republic of Korea.|Jilin Hospital Affiliated with Jilin University, Jilin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju 501-757, Republic of Korea.
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kee
authors.affiliation: The Second Hospital of Jilin University, Changchun, China.
authors.forename: Zhe Hao
authors.initials: ZH
authors.lastname: Piao
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju 501-757, Republic of Korea.
authors.forename: Jae Yeong
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju 501-757, Republic of Korea.
authors.forename: Gwi Ran
authors.initials: GR
authors.lastname: Kim
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju 501-757, Republic of Korea.
authors.forename: Sin Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju 501-757, Republic of Korea.|Yanbian University Hospital, 1327 Juzi Road, Yanbian, Jilin 133000, China.
authors.forename: Ming Quan
authors.initials: MQ
authors.lastname: Lin
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju 501-757, Republic of Korea.
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005355:Fibrosis; D005707:Gallic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D007545:Isoproterenol / Q000009:adverse effects*; D008297:Male; D051379:Mice; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D005707:Gallic Acid; D048056:Mitogen-Activated Protein Kinase 9; D007545:Isoproterenol