title: GH suppresses TGF-beta-mediated fibrosis and retains cardiac diastolic function.
abstract: The aims of this study were to elucidate the molecular mechanism by which growth hormone (GH) excess is anti-fibrotic in vitro and in vivo model. The in vivo model GH excess showed a significant increase of relative wall thickness with no concomitant disturbance of cardiac diastolic function. Western blot for extracellular matrix (ECM) structural proteins showed minimal change in the GH treatment group, compared to an Angiotensin II (Ang II) subpressor dose group. In cultured cardiac fibroblasts, we investigated the abundance of ECM proteins, phosphorylation of p38 mitogen-activated protein kinase (MAPK), and transforming growth factor-beta (TGF-beta)-specific transcriptional activity. GH down-regulated the expression of PAI-1 and fibronectin proteins activated by TGF-beta. In reporter assays, GH, but not insulin-like growth factor-1 (IGF-1), reduced TGF-beta-specific transcriptional activity. Moreover, GH markedly down-regulated TGF-beta-induced phosphorylation of p38 MAPK. These results demonstrated that a chronic excess of GH have an anti-fibrotic effect on cardiac remodeling, probably through a down-regulation of TGF-beta signaling via de-phosphorylation of p38 MAPK.
authors.affiliation: Department of Cardiovascular Medicine, Course of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Imanishi
authors.forename: Naoto
authors.initials: N
authors.lastname: Ashizawa
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtsuru
authors.forename: Shinji
authors.initials: S
authors.lastname: Seto
authors.forename: Yuri
authors.initials: Y
authors.lastname: Akiyama-Uchida
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawano
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kuroda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Saenko
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Katsusuke
authors.initials: K
authors.lastname: Yano
mesh_terms: D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003971:Diastole / Q000502:physiology*; D004452:Echocardiography; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D013006:Growth Hormone / Q000378:metabolism* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011920:Rats, Inbred WF; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D020782:Matrix Metalloproteinases