title: Resveratrol inhibits glucose-induced migration of vascular smooth muscle cells mediated by focal adhesion kinase.
abstract: METHODS
  Diabetes is a critical factor for atherosclerosis, as hyperglycemia induces vascular smooth muscle cell (VSMC) proliferation and migration and subsequently contributes to the formation of atherosclerotic lesions. This study investigates whether resveratrol plays a regulatory role in the proliferation and migration of VSMCs under high glucose induction to imitate a hyperglycemic condition.
  
  
  RESULTS
  Resveratrol inhibited the migration of VSMCs in the wound-healing assay and the formation of lamellipodia and filopodia as assessed by atomic force microscopy scanning. Resveratrol suppressed the mRNA expression of c-Src, Rac1, cdc42, IRS-1, MEKK1, MEKK4, and mitogen-activated protein kinase along with the protein levels of c-Src, p-Src, and cdc42 in VSMCs. Resveratrol decreased the level of p-FAK protein under normal glucose conditions. Resveratrol could inhibit the activities of matrix metalloproteinase (MMP) 2 and MMP 9 as shown by zymography. Moreover, resveratrol also regulated the mitogen-activated protein kinase pathway and MMP activities of VSMC migration under the high glucose condition.
  
  
  CONCLUSIONS
  The antimigratory effects of resveratrol by reduced MMP expression through the inhibition of Rac1, p-FAK, and lamellipodia formation and the activation of p-AKT and p-ERK1/2 suggest that resveratrol is a potential compound for the treatment of vascular diseases via the regulation of VSMC migration.
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan.
authors.forename: Yi-Chiao
authors.initials: YC
authors.lastname: Lin
authors.forename: Li-Hsuen
authors.initials: LH
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Varadharajan
authors.forename: May-Jywan
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Chia
authors.forename: Ta-Chun
authors.initials: TC
authors.lastname: Yuan
authors.forename: Ping-Jyun
authors.initials: PJ
authors.lastname: Sung
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Weng
mesh_terms: D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D005947:Glucose / Q000009:adverse effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018625:Microscopy, Atomic Force; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D013267:Stilbenes; D000081247:CSK Tyrosine-Protein Kinase; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D005947:Glucose; D000077185:Resveratrol
keywords: FAK; High glucose; Migration; Resveratrol; Vascular smooth muscle cell