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

Abstract β-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 β-cells through mostly unidentified secreted factors. Thus, we hypothesized that pericytes...

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Autores principales:	Lina Sakhneny, Alona Epshtein, Limor Landsman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/04c49dec808b409ab8df48674718bbbd
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spelling	oai:doaj.org-article:04c49dec808b409ab8df48674718bbbd2021-12-02T14:16:16ZPericytes contribute to the islet basement membranes to promote beta-cell gene expression10.1038/s41598-021-81774-82045-2322https://doaj.org/article/04c49dec808b409ab8df48674718bbbd2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81774-8https://doaj.org/toc/2045-2322Abstract β-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 β-cells through mostly unidentified secreted factors. Thus, we hypothesized that pericytes regulate β-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 β-cell physiology, including collagen IV, laminins, proteoglycans, fibronectin, nidogen, and hyaluronan. Compared to ECs, pancreatic pericytes produce significantly higher levels of α2 and α4 laminin chains, which constitute the peri-islet and vascular BM. We further found that the pericytic laminin isoforms differentially regulate mouse β-cells. Whereas α2 laminins promoted islet cell clustering, they did not affect gene expression. In contrast, culturing on Laminin-421 induced the expression of β-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 β-cell function.Lina SakhnenyAlona EpshteinLimor LandsmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lina Sakhneny Alona Epshtein Limor Landsman Pericytes contribute to the islet basement membranes to promote beta-cell gene expression
description	Abstract β-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 β-cells through mostly unidentified secreted factors. Thus, we hypothesized that pericytes regulate β-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 β-cell physiology, including collagen IV, laminins, proteoglycans, fibronectin, nidogen, and hyaluronan. Compared to ECs, pancreatic pericytes produce significantly higher levels of α2 and α4 laminin chains, which constitute the peri-islet and vascular BM. We further found that the pericytic laminin isoforms differentially regulate mouse β-cells. Whereas α2 laminins promoted islet cell clustering, they did not affect gene expression. In contrast, culturing on Laminin-421 induced the expression of β-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 β-cell function.
format	article
author	Lina Sakhneny Alona Epshtein Limor Landsman
author_facet	Lina Sakhneny Alona Epshtein Limor Landsman
author_sort	Lina Sakhneny
title	Pericytes contribute to the islet basement membranes to promote beta-cell gene expression
title_short	Pericytes contribute to the islet basement membranes to promote beta-cell gene expression
title_full	Pericytes contribute to the islet basement membranes to promote beta-cell gene expression
title_fullStr	Pericytes contribute to the islet basement membranes to promote beta-cell gene expression
title_full_unstemmed	Pericytes contribute to the islet basement membranes to promote beta-cell gene expression
title_sort	pericytes contribute to the islet basement membranes to promote beta-cell gene expression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/04c49dec808b409ab8df48674718bbbd
work_keys_str_mv	AT linasakhneny pericytescontributetotheisletbasementmembranestopromotebetacellgeneexpression AT alonaepshtein pericytescontributetotheisletbasementmembranestopromotebetacellgeneexpression AT limorlandsman pericytescontributetotheisletbasementmembranestopromotebetacellgeneexpression
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Pericytes contribute to the islet basement membranes to promote beta-cell gene expression

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