title: Aldosterone-induced osteopontin expression in vascular smooth muscle cells involves MR, ERK, and p38 MAPK.
abstract: Osteopontin (OPN) is known to be one of the cytokines that is involved in the vascular inflammation caused by aldosterone (Ald). Previous reports have shown that Ald increases OPN expression, and the mechanisms for this remain to be clarified. In this study, we investigated how Ald increases OPN expression in the vascular smooth muscle cells (VSMCs) of rats. Ald increased OPN expression time dependently as well as dose dependently. This increase was diminished by spironolactone, a mineralocorticoid receptor (MR) antagonist. PD98059, an inhibitor of p42/44 MAPK pathway, and SB203580, an inhibitor of p38 MAPK pathway, suppressed Ald-induced OPN expression and secretion in VSMCs. VSMCs migration stimulated by aldosterone required OPN expression. In conclusion, these data suggest that Ald-induced OPN expression in VSMC is mediated by MR and signaling cascades involving ERK and p38 MAPK. These molecules may represent therapeutic targets for the prevention of pathological vascular remodeling.
authors.affiliation: Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yi Shan Road, Shanghai, 200233, People's Republic of China.
authors.forename: Guo-Xiang
authors.initials: GX
authors.lastname: Fu
authors.forename: Chan-Chan
authors.initials: CC
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhong
authors.forename: Ding-Liang
authors.initials: DL
authors.lastname: Zhu
authors.forename: Ping-Jin
authors.initials: PJ
authors.lastname: Gao
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D015153:Blotting, Western; D020212:Carotid Artery Injuries / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D058426:Neointima / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D053495:Osteopontin / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016376:Oligonucleotides, Antisense; D018161:Receptors, Mineralocorticoid; D053495:Osteopontin; D000450:Aldosterone; D008156:Luciferases; D048051:p38 Mitogen-Activated Protein Kinases