title: Calcitonin gene-related peptide regulates mitogen-activated protein kinase pathway to decrease transforming growth factor β1-induced hepatic plasminogen activator inhibitor-1 mRNA expression in HepG2 cells.
abstract: Transforming growth factor (TGF) β1-induced plasminogen activator inhibitor (PAI)-1 is one of factors associated with the development of hepatic fibrosis. Calcitonin gene-related peptide (CGRP) shows hepatoprotective effect during hepatic injuries, including fibrosis. However, the effects of CGRP on PAI-1 expression induced by TGFβ1 are unknown. In this study, we investigated the effect of CGRP on TGFβ1-induced PAI-1 expression and its regulatory mechanisms in HepG2 cells. CGRP inhibited TGFβ1-induced PAI-1 expression. H89, a protein kinase A inhibitor, abolished the inhibition of TGFβ1-induced PAI-1 expression by CGRP. TGFβ1 activated mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase, c-jun NH2-terminal kinase, and p38, and this activation was abolished by CGRP. These results show that the CGRP-induced cAMP/PKA activation suppresses activation of MAPK induced by TGFβ1, leading to decreased PAI-1 expression in HepG2 cells.
authors.affiliation: a Faculty of Applied Bioscience, Department of Nutritional Science , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Matsui
authors.forename: Takumi
authors.initials: T
authors.lastname: Yamane
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kobayashi-Hattori
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oishi
mesh_terms: D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D007546:Isoquinolines; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D013449:Sulfonamides; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D020928:Mitogen-Activated Protein Kinases; D015740:Calcitonin Gene-Related Peptide; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: calcitonin gene-related peptide; hepatocytes; mitogen-activated protein kinase pathway; plasminogen activator inhibitor-1; transforming growth factor β1