title: Inhibitory effects of resveratrol on PDGF-BB-induced retinal pigment epithelial cell migration via PDGFRβ, PI3K/Akt and MAPK pathways.
abstract: OBJECTIVE
  In diseases such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, and age-related macular degeneration, retinal pigment epithelial (RPE) cells proliferate and migrate. Moreover, platelet-derived growth factor (PDGF) has been shown to enhance proliferation and migration of RPE cells in PVR. Even resveratrol can suppress the migration and adhesion of many cell types, its effects on RPE cell migration and adhesion remain unknown. In this study, we investigated the inhibitory effects of resveratrol on RPE cell migration induced by PDGF-BB, an isoform of PDGF, and adhesion to fibronectin, a major ECM component of PVR tissue.
  
  
  METHODS
  The migration of RPE cells was assessed by an electric cell-substrate impedance sensing migration assay and a Transwell migration assay. A cell viability assay was used to determine the viability of resveratrol treated-cells. The cell adhesion to fibronectin was examined by an adhesion assay. The interactions of resveratrol with PDGF-BB were analyzed by a dot binding assay. The PDGF-BB-induced signaling pathways were determined by western blotting and scratch wound healing assay.
  
  
  RESULTS
  Resveratrol inhibited PDGF-BB-induced RPE cell migration in a dose-dependent manner, but showed no effects on ARPE19 cell adhesion to fibronectin. The cell viability assay showed no cytotoxicity of resveratrol on RPE cells and the dot binding assay revealed no direct interactions of resveratrol with PDGF-BB. Inhibitory effects of resveratrol on PDGF-BB-induced platelet-derived growth factor receptor β (PDGFRβ) and tyrosine phosphorylation and the underlying pathways of PI3K/Akt, ERK and p38 activation were found; however, resveratrol and PDGF-BB showed no effects on PDGFRα and JNK activation. Scratch wound healing assay demonstrated resveratrol and the specific inhibitors of PDGFR, PI3K, MEK or p38 suppressed PDGF-BB-induced cell migration.
  
  
  CONCLUSIONS
  These results indicate that resveratrol is an effective inhibitor of PDGF-BB-induced RPE cell migration via PDGFRβ, PI3K/Akt and MAPK pathways, but has no effects on the RPE cell adhesion to fibronectin.
authors: Department of Ophthalmology, Cardinal Tien Hospital, New Taipei City, Taiwan.
authors: Chi-Ming
authors: CM
authors: Chan
authors: Hsun-Hsien
authors: HH
authors: Chang
authors: Vin-Chi
authors: VC
authors: Wang
authors: Chuen-Lin
authors: CL
authors: Huang
authors: Chi-Feng
authors: CF
authors: Hung
mesh_terms: D000077214:Becaplermin; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D000077185:Resveratrol; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D013267:Stilbenes; D000077214:Becaplermin; D019869:Phosphatidylinositol 3-Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol