Interazione tra B1-INTEGRINA e SEL1L nello sviluppo del pancreas

Beta1-Integrin and SEL1L interaction in pancreas development Diaferia Giuseppe In the present study we looked at the role of beta1-integrin and SEL1L in beta-cell differentiation through ECM interaction. Using beta-cell specific beta1-integrin KO we showed a dramatic defect in cell-adhesion on extracellular matrixes and a marked reduction in beta-cell mass due to a defect in beta-cell proliferation confirmed by the loss of cyclin D1 expression and the upregulation of the inhibitors p21 and p27. In contrast glucose tolerance was enhanced due to the increased insulin sensitivity. Using an in vitro model of human pancreas development we found SEL1L highly expressed in the developing islet cell clusters and at the basal membrane of undifferentiated acini of the fetal pancreatic tissue while restricted to islet cells in the adult pancreas. In vitro expansion of fetal and adult islet cell clusters on extracellular matrixes as netrin-1 led to a significative upregulation of insulin and PDX-1 expression as well as SEL1L. Coimmunoprecipitation experiments of SEL1L with beta1-integrin suggest that this effect, mediated by ECM, are likely to be integrin dependent. These results point to the essential role of beta1 integrin and SEL1L signaling in pancreatic cell development and proliferation