title: Up-regulation of TGF-β via the activation of extracellular signal-regulated             kinase 1 and 2 induced by prorenin in human renal mesangial cells.
abstract: Prorenin is thought to be an inactive precursor of renin. This study investigated whether human prorenin was capable of activating the (pro)renin receptors [(P)RRs], leading to the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured human renal mesangial cells (HRMCs). HRMCs cultured in vitro were pretreated with an AT1 and AT2 blocker prior to stimulation by prorenin, PD98059 (an inhibitor of ERK1/2) and handle-region peptide (HRP). Phosphorylated ERK1/2 was evaluated using Western blot analysis, and the concentration of TGF-β was measured by ELISA. The mRNA of TGF-β was evaluated by RT-PCR. It was found that prorenin activated the (P)RR in cultured HRMCs, which in turn increased p-ERK1/2. Prorenin induced rapid phosphorylation of ERK1/2 and increased p-ERK1/2 in a time- and dose-dependent manner. The protein levels of TGF-β increased significantly with the stimulation of prorenin. PD98059 significantly decreased p-ERK1/2 and then downregulated TGF-β. HRP did not inhibit either ERK1/2 phosphorylation or the increase in TGF-β. ERK1/2 phosphorylation induced by prorenin led to a marked increase in TGF-β. The regulation of TGF-β was highly dependent on ERK1/2. Thus, ERK1/2 may play a key role in the development of kidney disease. HRP neither affects the ERK1/2 signaling nor the level of TGF-β in HRMCs.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning116011, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Jia
authors.forename: Lili
authors.initials: L
authors.lastname: Ren
authors.forename: Yumei
authors.initials: Y
authors.lastname: Mi
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Yinong
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D050527:Mesangial Cells / Q000166:cytology / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D012083:Renin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D000093342:Prorenin Receptor
chemical_list: D020536:Enzyme Activators; D005419:Flavonoids; D009842:Oligopeptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D012083:Renin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000093342:Prorenin Receptor