The study of genes governing pancreas development could help the advancement of cell-replacement therapies for diabetes. SEL1L, a component of the endoplasmic reticulum associated degradation (ERAD) pathway, has been reported to regulate: (i) the differentiation of the pancreatic endocrine and exocrine tissue during the secondary transition of mouse embryonic development (Li et al., Dev Bio 2010), (ii) the neural stem cell self-renewal and lineage commitment (Cardano et al., JBC 2011), and (iii) cell cycle progression through regulation of genes related to cell-matrix interaction (Cattaneo et al., Neoplasia 2005). Here, we show that SEL1L expression is developmentally regulated, such that it is expressed in developing islet cells and in nascent acinar clusters adjacent to basement membranes, whereas in the adult pancreas it becomes restricted to the islets of Langherans. This expression pattern, together with the identification of two inverse RGD motifs in the fibronectin type II domain of SEL1L, led us to investigate its possible interaction with cell adhesion molecules to regulate islets architecture. Co-immunoprecipitation studies revealed an interaction between SEL1L and ß1-integrin, while down-modulation of SEL1L in pancreatic ß-cells negatively influences cell adhesion on selected matrix components. Furthermore, the absence of SEL1L protein strongly inhibits glucose-stimulated insulin secretion in isolated mouse pancreatic islets unveiling an important role of SEL1L in insulin trafficking. These results provide preliminary insights into the cross-talk between extracellular matrix and insulin signalling in creating a favourable micro-environment for ß-cell development and function.
SEL1L in pancreas development and ß-cell function / G. Diaferia, M. Cardano, M. Cattaneo, P. DeBlasio, V. Cirulli, I. Biunno. ((Intervento presentato al 7. convegno European Summer School on Stem Cells & Regenerative Medicine tenutosi a Hydra nel 2011.
|Titolo:||SEL1L in pancreas development and ß-cell function|
DIAFERIA, GIUSEPPE (Primo)
CARDANO, MARINA (Secondo)
|Data di pubblicazione:||set-2011|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Citazione:||SEL1L in pancreas development and ß-cell function / G. Diaferia, M. Cardano, M. Cattaneo, P. DeBlasio, V. Cirulli, I. Biunno. ((Intervento presentato al 7. convegno European Summer School on Stem Cells & Regenerative Medicine tenutosi a Hydra nel 2011.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|