title: Mediation of the migration of endothelial cells and fibroblasts on polyurethane nanocomposites by the activation of integrin-focal adhesion kinase signaling.
abstract: Model surfaces of polyurethane-gold nanocomposites (PU-Au) were used to examine cell behavior on nanophase-segregated materials. Previously we showed that endothelial cell (EC) migration on these materials was modulated by the PI3K/Akt/eNOS pathway. The present study, investigated the expressions of alpha5/beta3 (α5β3) integrin, focal adhesion kinase (FAK), and other downstream signal molecules such as the Rho family and matrix metalloproteinases 2 (MMP-2) induced by the materials in two different cells, that is bovine arterial endothelial cells (BAEC) and human skin fibroblasts (HSF). Both cells proliferated better on the more phase-separated PU-Au 43.5 ppm than on the less phase-separated controls (PU and PU-Au 174 ppm). On PU-Au 43.5 ppm, BAEC compared to HSF had denser actin fibers and were more extended. BAEC became rounded with Y-27632 treatment and shrunk with LY294002 treatment. Treatment by inhibitors only caused slight changes in HSF. The migration distance of BAEC on PU-Au 43.5 ppm was greater than that of HSF, and was significantly reduced by LY294002 or Y-27632 but not SU-1498. The expressions of p-FAK, p-RhoA, p-Rac/Cdc42, MMP2, and α5β3 integrin induced by PU-Au 43.5 ppm were more pronounced in BAEC versus HSF. Further enhancement in MMP2 and α5β3 integrin expressions by FAK-GFP transfection was more remarkable for cells on PU-Au 43.5 ppm. Our findings suggested that the integrin α5β3/FAK pathway may be induced by nanophase-separated materials in both ECs and fibroblasts to promote their proliferation/migration, while the crosstalk between the PI3K/Akt/eNOS pathway and FAK/Rho-GTPase activation may account for the greater effect in ECs than in fibroblasts.
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China. shhsu@ntu.edu.tw
authors.forename: Huey-Shan
authors.initials: HS
authors.lastname: Hung
authors.forename: Mei-Yun
authors.initials: MY
authors.lastname: Chu
authors.forename: Chien-Hsun
authors.initials: CH
authors.lastname: Lin
authors.forename: Chia-Ching
authors.initials: CC
authors.lastname: Wu
authors.forename: Shan-hui
authors.initials: SH
authors.lastname: Hsu
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000166:cytology; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006046:Gold; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D053761:Nanocomposites / Q000737:chemistry* / Q000648:ultrastructure; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011140:Polyurethanes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000166:cytology; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D016023:Integrins; D011140:Polyurethanes; D049452:Green Fluorescent Proteins; D006046:Gold; D052250:Nitric Oxide Synthase Type III; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein