Pericytes contribute to the islet basement membranes to promote beta-cell gene expression.

ABSTRACT: ?-Cells depend on the islet basement membrane (BM). While some islet BM components are produced by endothelial cells (ECs), the source of others remains unknown. Pancreatic pericytes directly support ?-cells through mostly unidentified secreted factors. Thus, we hypothesized that pericytes regulate ?-cells through the production of BM components. Here, we show that pericytes produce multiple components of the mouse pancreatic and islet interstitial and BM matrices. Several of the pericyte-produced ECM components were previously implicated in ?-cell physiology, including collagen IV, laminins, proteoglycans, fibronectin, nidogen, and hyaluronan. Compared to ECs, pancreatic pericytes produce significantly higher levels of ?2 and ?4 laminin chains, which constitute the peri-islet and vascular BM. We further found that the pericytic laminin isoforms differentially regulate mouse ?-cells. Whereas ?2 laminins promoted islet cell clustering, they did not affect gene expression. In contrast, culturing on Laminin-421 induced the expression of ?-cell genes, including Ins1, MafA, and Glut2, and significantly improved glucose-stimulated insulin secretion. Thus, alongside ECs, pericytes are a significant source of the islet BM, which is essential for proper ?-cell function.

SUBMITTER: Sakhneny L 

PROVIDER: S-EPMC7840750 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature