The vascular basement membrane: a niche for insulin gene expression and Beta cell proliferation.
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.
Nikolova
Ganka
G
Max-Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Jabs
Normund
N
Konstantinova
Irena
I
Domogatskaya
Anna
A
Tryggvason
Karl
K
Sorokin
Lydia
L
Fässler
Reinhard
R
Gu
Guoqiang
G
Gerber
Hans-Peter
HP
Ferrara
Napoleone
N
Melton
Douglas A
DA
Lammert
Eckhard
E
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
D007328:Insulin; D019012:Integrin beta1; D007797:Laminin; D042461:Vascular Endothelial Growth Factor A