title: Insulin-independent GLUT4 translocation in proliferative vascular smooth muscle cells involves SM22α.
abstract: The insulin-sensitive glucose transporter 4 (GLUT4) is a predominant facilitative glucose transporter in vascular smooth muscle cells (VSMCs) and is significantly upregulated in rabbit neointima. This study investigated the role of GLUT4 in VSMC proliferation, the cellular mechanism underlying PDGF-BB-stimulated GLUT4 translocation, and effects of SM22α, an actin-binding protein, on this process. Chronic treatment of VSMCs with PDGF-BB significantly elevated GLUT4 expression and glucose uptake. PDGF-BB-induced VSMC proliferation was dependent on GLUT4-mediated glucose uptake. Meanwhile, the response of GLUT4 to insulin decreased in PDGF-BB-stimulated VSMCs. PDGF-BB-induced GLUT4 translocation partially rescued glucose utilization in insulin-resistant cells. Immunofluorescence and western blot analysis revealed that PDGF-BB induced GLUT4 translocation in an actin dynamics-dependent manner. SM22α disruption facilitated GLUT4 translocation and glucose uptake by promoting actin dynamics and cortical actin polymerization. Similar results were observed in VSMCs of SM22α-/-mice. The in vivo experiments showed that the glucose level in the neointima induced by ligation was significantly increased in SM22α-/-mice, accompanied by increased neointimal thickness, compared with those in wild-type mice. These findings suggest that GLUT4-mediated glucose uptake is involved in VSMC proliferation, and provide a novel link between SM22α and glucose utilization in PDGF-BB-triggered proliferation.
  
  
  
  • GLUT4-mediated glucose uptake is required for the VSMC proliferation. • PDGF-BB-induced GLUT4 translocation partially rescues glucose uptake in insulin resistance. • SM22α disruption enhances PDGF-BB-induced GLUT4 translocation. • Glucose level in injured vascular tissue is positively correlated with neointimal hyperplasia.
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Xie
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Yong-Qing
authors.initials: YQ
authors.lastname: Dou
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Nie
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Pin
authors.initials: P
authors.lastname: Lv
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Li
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Sui-Bing
authors.initials: SB
authors.lastname: Miao
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Yin
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Dong
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Song
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Shu
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China. hanmei@hebmu.edu.cn.
authors.forename: Mei
authors.identifier: 0000-0003-2696-6359
authors.initials: M
authors.lastname: Han
mesh_terms: D000199:Actins / Q000378:metabolism; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D000077214:Becaplermin; D020212:Carotid Artery Injuries / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D058426:Neointima / Q000378:metabolism*; D058105:Polymerization; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000199:Actins; D043925:Angiogenesis Inducing Agents; D004268:DNA-Binding Proteins; C528734:GLUT4 enhancer factor, mouse; D007328:Insulin; D008840:Microfilament Proteins; D009124:Muscle Proteins; D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; C058992:Tagln protein, mouse; D014157:Transcription Factors; D000077214:Becaplermin; D005947:Glucose
keywords: GLUT4; Glucose uptake; Proliferation; SM22α; VSMCs