β1 integrin-extracellular matrix interactions are essential for maintaining exocrine pancreas architecture and function

Integrin receptors are responsible for integrating extracellular matrix signals inside the cell. The most prominent integrin receptor, beta 1 integrin, has a role in cell function, survival and differentiation. Recently, we demonstrated a profound in vivo role of beta 1 integrin expression in the pancreas on glucose homeostasis and islet function. Here, we extend these results by examining the role of beta 1 integrin in exocrine pancreatic structure and function. Adult C57Bl/6 mice hemizygous for a collagen type I alpha 2 (Col1 alpha 2) promoter-controlled tamoxifen-inducible Cre recombinase gene and homozygous for loxP-beta 1 integrin were injected with tamoxifen or corn oil to generate mice deleted or not for beta 1 integrin. Pancreata derived from these male mice were analyzed by quantitative reverse transcriptase-polymerase chain reaction, western blot and immunofluorescence. Our results showed that beta 1 integrin-deficient mice displayed a significant decrease in pancreas weight with a significant reduction of amylase, regenerating islet-derived protein II and carboxypeptidase-A expression (P<0.05-0.01). Compared with control pancreata, beta 1 integrin-deficient pancreata showed reduced mRNA expression of extracellular matrix (collagen type I alpha 2, fibronectin and laminin) genes (P<0.05), detached acini clusters and lost focal adhesion structure. Moreover, beta 1 integrin-deficient pancreatic acinar cells displayed decreased proliferation (P<0.05) and increased apoptosis (P<0.001). Apoptosis was reduced to that of controls when isolated exocrine clusters were cultured in media supplemented with extracellular matrix proteins. Taken together, these results implicate beta 1 integrin as an essential component for maintaining exocrine pancreatic structure and function. Laboratory Investigation (2013) 93, 31-40; doi: 10.1038/labinvest.2012.147; published online 15 October 2012