The vascular basement membrane: a niche for insulin gene expression and Beta cell proliferation.

Nikolova G, Jabs N, Konstantinova I, Domogatskaya A, Tryggvason K, Sorokin L, Fässler R, Gu G, Gerber HP, Ferrara N, Melton DA, Lammert E
Dev Cell. 2006 10 (3): 397-405

PMID: 16516842 · DOI:10.1016/j.devcel.2006.01.015

Endocrine pancreatic beta cells require endothelial signals for their differentiation and function. However, the molecular basis for such signals remains unknown. Here, we show that beta cells, in contrast to the exocrine pancreatic cells, do not form a basement membrane. Instead, by using VEGF-A, they attract endothelial cells, which form capillaries with a vascular basement membrane next to the beta cells. We have identified laminins, among other vascular basement membrane proteins, as endothelial signals, which promote insulin gene expression and proliferation in beta cells. We further demonstrate that beta1-integrin is required for the beta cell response to the laminins. The proposed mechanism explains why beta cells must interact with endothelial cells, and it may apply to other cellular processes in which endothelial signals are required.

MeSH Terms (15)

Animals Basement Membrane Blood Vessels Cell Line Cell Proliferation Endothelial Cells Gene Expression Regulation Insulin Insulin-Secreting Cells Integrin beta1 Laminin Mice Pancreas Signal Transduction Vascular Endothelial Growth Factor A

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