ß1 integrin is a crucial regulator of pancreatic ß-cell expansion.
Development
; 140(16): 3360-72, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23863477
ABSTRACT
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 ß1 integrin gene in developing pancreatic ß-cells reduces their ability to expand during embryonic life, during the first week of postnatal life, and thereafter. Mice lacking ß1 integrin in insulin-producing cells exhibit a dramatic reduction of the number of ß-cells to only â¼18% of wild-type levels. Despite the significant reduction in ß-cell mass, these mutant mice are not diabetic. A thorough phenotypic analysis of ß-cells lacking ß1 integrin revealed a normal expression repertoire of ß-cell markers, normal architectural organization within islet clusters, and a normal ultrastructure. Global gene expression analysis revealed that ablation of this ECM receptor in ß-cells inhibits the expression of genes regulating cell cycle progression. Collectively, our results demonstrate that ß1 integrin receptors function as crucial positive regulators of ß-cell expansion.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica no Desenvolvimento
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Integrina beta1
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Proliferação de Células
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Células Secretoras de Insulina
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article