title: Fibrin improves beta (INS-1) cell function, proliferation and survival through integrin αvβ3.
abstract: Extracellular matrix (ECM)-integrin stimulation can promote beta cell differentiation, proliferation and function. However, beta cells lose their insulin secretion function in response to glucose stimulation, and senesce when cultured with ECM proteins for a long time. Fibrin is a provisional ECM protein that is capable of maintaining beta cell function, yet the mechanisms by which this occurs is unknown. The present study examined how fibrin interacts with integrin receptors to promote beta cell cluster formation, proliferation and function. The rat insulinoma cell line, INS-1, was cultured on tissue-culture polystyrene, or with 2-D or 3-D fibrin gels for up to 4 weeks. Cells cultured with fibrin formed islet-like clusters and showed direct contacts with fibrin determined by scanning electron microscopy. Fibrin-cultured INS-1 cells also had significantly increased glucose-stimulated insulin secretion. A significant increase in integrin αvβ3 protein and phosphorylated FAK, Erk1/2 and Akt levels was observed in fibrin-cultured INS-1 cells, which was associated with significantly increased cell proliferation and decreased cell apoptosis. Integrin αvβ3 blockade affected INS-1 cell spreading on fibrin gels, and resulted in significantly decreased FAK phosphorylation and increased cleaved caspase-3 levels. These results show that fibrin promotes beta cell function, proliferation and survival via integrin αvβ3 interactions.
authors.affiliation: Children's Health Research Institute, 800 Commissioners Road East, London, Ontario N6C 2V5, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Riopel
authors.forename: William
authors.initials: W
authors.lastname: Stuart
authors.forename: Rennian
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005337:Fibrin / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D039302:Integrin alphaVbeta3; D005337:Fibrin
keywords: Beta cell; Cell signaling; Diabetes; Fibrin; Integrin