Expression and function of αβ1 integrins in pancretic beta (INS-1) cells (original) (raw)
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Β1 Integrin is a Crucial Regulator of Pancreatic Β-Cell Expansion
Development, 2013
Development of the endocrine compartment of the pancreas, as represented by the islets of Langerhans, occurs through a series of highly regulated events encompassing branching of the pancreatic epithelium, delamination and differentiation of islet progenitors from ductal domains, followed by expansion and three-dimensional organization into islet clusters. Cellular interactions with the extracellular matrix (ECM) mediated by receptors of the integrin family are postulated to regulate key functions in these processes. Yet, specific events regulated by these receptors in the developing pancreas remain unknown. Here, we show that ablation of the β1 integrin gene in developing pancreatic β-cells reduces their ability to expand during embryonic life, during the first week of postnatal life, and thereafter. Mice lacking β1 integrin in insulin-producing cells exhibit a dramatic reduction of the number of β-cells to only ~18% of wild-type levels. Despite the significant reduction in β-cell mass, these mutant mice are not diabetic. A thorough phenotypic analysis of β-cells lacking β1 integrin revealed a normal expression repertoire of β-cell markers, normal architectural organization within islet clusters, and a normal ultrastructure. Global gene expression analysis revealed that ablation of this ECM receptor in β-cells inhibits the expression of genes regulating cell cycle progression. Collectively, our results demonstrate that β1 integrin receptors function as crucial positive regulators of β-cell expansion.
Diabetes, 2005
The integrin receptors play a major role in tissue morphogenesis and homeostasis by regulating cell interactions with extracellular matrix proteins. We have examined the expression pattern of integrin subunits in the human fetal pancreas (8-20 weeks fetal age) and the relevance of beta1 integrin function for insulin gene expression and islet cell survival. Its subunits alpha3, alpha5, and alpha6 beta1 integrins are expressed in ductal cells at 8 weeks, before glucagon- and insulin-immunoreactive cells bud off; their levels gradually increase in both ductal cells and islet clusters up to 20 weeks. Colocalization of alpha3, alpha5 and alpha6 beta1 integrins with endocrine cell markers was frequently observed in 8- to 20-week fetal pancreatic cells. When the beta1 integrin receptor was functionally blocked in cultured islet-epithelial clusters with a beta1 immunoneutralizing antibody or following transient beta1 integrin small interfering RNA treatment, there was inhibition of cell adh...
Laboratory Investigation, 2013
Integrin receptors are responsible for integrating extracellular matrix signals inside the cell. The most prominent integrin receptor, b1 integrin, has a role in cell function, survival and differentiation. Recently, we demonstrated a profound in vivo role of b1 integrin expression in the pancreas on glucose homeostasis and islet function. Here, we extend these results by examining the role of b1 integrin in exocrine pancreatic structure and function. Adult C57Bl/6 mice hemizygous for a collagen type Ia2 (Col1a2) promoter-controlled tamoxifen-inducible Cre recombinase gene and homozygous for loxP-b1 integrin were injected with tamoxifen or corn oil to generate mice deleted or not for b1 integrin. Pancreata derived from these male mice were analyzed by quantitative reverse transcriptase-polymerase chain reaction, western blot and immunofluorescence. Our results showed that b1 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 (Po0.05-0.01). Compared with control pancreata, b1 integrin-deficient pancreata showed reduced mRNA expression of extracellular matrix (collagen type Ia2, fibronectin and laminin) genes (Po0.05), detached acini clusters and lost focal adhesion structure. Moreover, b1 integrin-deficient pancreatic acinar cells displayed decreased proliferation (Po0.05) and increased apoptosis (Po0.001). 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 b1 integrin as an essential component for maintaining exocrine pancreatic structure and function.
Expression and Function of αvβ3 and αvβ5 Integrins in the Developing Pancreas
The Journal of Cell Biology, 2000
Cell–cell and cell–matrix interactions play a critical role in tissue morphogenesis and in homeostasis of adult tissues. The integrin family of adhesion receptors regulates cellular interactions with the extracellular matrix, which provides three-dimensional information for tissue organization. It is currently thought that pancreatic islet cells develop from undifferentiated progenitors residing within the ductal epithelium of the fetal pancreas. This process involves cell budding from the duct, migration into the surrounding mesenchyme, differentiation, and clustering into the highly organized islet of Langerhans. Here we report that αvβ3 and αvβ5, two integrins known to coordinate epithelial cell adhesion and movement, are expressed in pancreatic ductal cells and clusters of undifferentiated cells emerging from the ductal epithelium. We show that expression and function of αvβ3 and αvβ5 integrins are developmentally regulated during pancreatic islet ontogeny, and mediate adhesion ...