title: The vascular basement membrane: a niche for insulin gene expression and Beta cell proliferation.
abstract: 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.
authors.affiliation: Max-Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Ganka
authors.initials: G
authors.lastname: Nikolova
authors.forename: Normund
authors.initials: N
authors.lastname: Jabs
authors.forename: Irena
authors.initials: I
authors.lastname: Konstantinova
authors.forename: Anna
authors.initials: A
authors.lastname: Domogatskaya
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Gu
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Gerber
authors.forename: Napoleone
authors.initials: N
authors.lastname: Ferrara
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Melton
authors.forename: Eckhard
authors.initials: E
authors.lastname: Lammert
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000166:cytology / Q000378:metabolism*; D001808:Blood Vessels / Q000033:anatomy & histology*; D002460:Cell Line; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D007328:Insulin; D019012:Integrin beta1; D007797:Laminin; D042461:Vascular Endothelial Growth Factor A