title: DIM attenuates TGF-β1-induced myofibroblast differentiation in neonatal rat cardiac fibroblasts.
abstract: 3,3'-Diindolylmethane (DIM) is a natural component of cruciferous plants. Previous studies have shown that DIM has multiple physiological effects including anti-angiogenic, anti-inflammatory and anti-cancer effect. However, little is known about the role of DIM on myofibroblast differentiation and extracellular matrix (ECM) production. This study investigated the effect of DIM on myofibroblast differentiation and ECM production in neonatal rat cardiac fibroblasts induced by transforming growth factor β1 (TGF-β1). We found that DIM blunted TGF-β1 induced conversion of cardiac fibroblast into myofibroblast, and reduced the mRNA and protein expressions of α-smooth muscle actin (α-SMA). Furthermore, DIM also significantly decreased the mRNA expression of fibrosis markers (Collagen I, Collagen III, connective tissue growth factor (CTGF) in neonatal rat cardiac fibroblasts induced by TGF-β1. DIM attenuated the phosphorylation AKT and glycogen synthase kinase-3β (GSK-3β) induced by TGF-β1. Our results showed that DIM was a potential drug to attenuate myofibroblast differentiation and excessive ECM production induced by TGF-β1 through down-regulated AKT/GSK-3β signaling pathways.
authors.affiliation: Department of cardiology, Renmin Hospital of Wuhan University Wuhan 430060, China ; Cardiovascualar Research Institute of Wuhan University Wuhan 430060, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of cardiology, Renmin Hospital of Wuhan University Wuhan 430060, China ; Cardiovascualar Research Institute of Wuhan University Wuhan 430060, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of cardiology, Renmin Hospital of Wuhan University Wuhan 430060, China ; Cardiovascualar Research Institute of Wuhan University Wuhan 430060, China ; Department of Xiangyang Hospital, Hubei University of Medicine Xiangyang 441000, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiao
authors.affiliation: Department of cardiology, Renmin Hospital of Wuhan University Wuhan 430060, China ; Cardiovascualar Research Institute of Wuhan University Wuhan 430060, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of cardiology, Renmin Hospital of Wuhan University Wuhan 430060, China ; Cardiovascualar Research Institute of Wuhan University Wuhan 430060, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of cardiology, Renmin Hospital of Wuhan University Wuhan 430060, China ; Cardiovascualar Research Institute of Wuhan University Wuhan 430060, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of cardiology, Renmin Hospital of Wuhan University Wuhan 430060, China ; Cardiovascualar Research Institute of Wuhan University Wuhan 430060, China.
authors.forename: Zhefu
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of cardiology, Renmin Hospital of Wuhan University Wuhan 430060, China ; Cardiovascualar Research Institute of Wuhan University Wuhan 430060, China.
authors.forename: Shizhao
authors.initials: S
authors.lastname: Xiang
authors.affiliation: Department of cardiology, Renmin Hospital of Wuhan University Wuhan 430060, China ; Cardiovascualar Research Institute of Wuhan University Wuhan 430060, China.
authors.forename: Qizhu
authors.initials: Q
authors.lastname: Tang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006321:Heart / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; D055513:Connective Tissue Growth Factor; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D007211:Indoles; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C526316:CCN2 protein, rat; C498862:Acta2 protein, rat; C000605508:Gsk3b protein, rat; C016392:3,3'-diindolylmethane
keywords: AKT; DIM; GSK3β; cardiac fibrosis; myofibroblast