title: GSTpi protects against angiotensin II-induced proliferation and migration of vascular smooth muscle cells by preventing signal transducer and activator of transcription 3 activation.
abstract: Angiotensin II (Ang II)-elicited excessive proliferation, hypertrophy and migration of vascular smooth muscle cells (VSMCs) are vital to the pathogenesis of atheroclerosis. Glutathione S-transferase pi (GSTpi) exists extensively in various kinds of cells and protects cells against different stresses. However, knowledge remains limited about what GSTpi acts in VSMCs. We investigated the effect of GSTpi on Ang II-induced VSMC proliferation, hypertrophy and migration and its latent mechanism. Overexpression and RNAi experiments demonstrated that GSTpi inhibited Ang II-induced proliferation, hypertrophy and migration of VSMCs and arrested progression of cell cycle from G0/G1 to S phase. Immunoprecipitation, mass spectrometry and confocal microscopy analyses showed that GSTpi directly associated with signal transducer and activator of transcription 3 (STAT3) to prevent Ang II-triggered binding of Src to STAT3 and thus suppressed Ang II-stimulated phosphorylation and nuclear translocation of STAT3, as well as cyclin D1 expression. In contrast, GSTpi didn't affect Ang II-activated extracellular signal-regulated kinase (ERK1/2). GSTpi acts as a negative regulator to prevent Ang II-triggered proliferative signaling in VSMCs, suggesting that it may protect vessels against the stresses associated with atherosclerosis formation.
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, People's Republic of China.
authors: Dan
authors: D
authors: Chen
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, People's Republic of China.
authors: Jinjiao
authors: J
authors: Liu
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, People's Republic of China.
authors: Bing
authors: B
authors: Rui
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, People's Republic of China.
authors: Min
authors: M
authors: Gao
authors: School of Biotechnology, Royal Institute of Technology, No. 21, Roslagstullsbacken, Stockholm SE-10691, Sweden.
authors: Ningwei
authors: N
authors: Zhao
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, People's Republic of China.
authors: Shuai
authors: S
authors: Sun
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, People's Republic of China.
authors: Aijing
authors: A
authors: Bi
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, People's Republic of China.
authors: Tingting
authors: T
authors: Yang
authors: Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210046, People's Republic of China.
authors: Yingtao
authors: Y
authors: Guo
authors: Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210046, People's Republic of China. Electronic address: yinzhimin@njnu.edu.cn.
authors: Zhimin
authors: Z
authors: Yin
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210097, People's Republic of China. Electronic address: lanluo@nju.edu.cn.
authors: Lan
authors: L
authors: Luo
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D051549:Glutathione S-Transferase pi / Q000378:metabolism*; D006984:Hypertrophy; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D050796:STAT3 Transcription Factor; D000804:Angiotensin II; D051549:Glutathione S-Transferase pi; D019061:src-Family Kinases
keywords: 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide; Ang II; Angiotensin II; DMSO; GSH; GSTpi; Glutathione S-transferase pi; JAK2; JNK; Janus-activated kinase 2; MTT; PBS; STAT3; Signal transducer and activator of transcription 3; TLK199; TNF-α; TRAF2; VSMCs; Vascular smooth muscle cells; angiotensin II; c-Jun NH2-terminal kinases; dimethylsulfoxide; g-glutamyl-S-(benzyl) cysteinyl-R-phenyl glycine diethyl ester; glutathione; glutathione S-transferase pi; phosphate buffered solution; signal transducer and activator of transcription 3; tumor necrosis factor alpha; tumor necrosis factor receptor-associated factor 2; vascular smooth muscle cells