Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration

Abstract Endogenous β cell regeneration could alleviate diabetes, but proliferative stimuli within the islet microenvironment are incompletely understood. We previously found that β cell recovery following hypervascularization-induced β cell loss involves interactions with endothelial cells (ECs) an...

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Autores principales:	Diane C. Saunders, Kristie I. Aamodt, Tiffany M. Richardson, Alexander J. Hopkirk, Radhika Aramandla, Greg Poffenberger, Regina Jenkins, David K. Flaherty, Nripesh Prasad, Shawn E. Levy, Alvin C. Powers, Marcela Brissova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/9fc6488438814df2a6871457cb867bcb
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spelling	oai:doaj.org-article:9fc6488438814df2a6871457cb867bcb2021-12-02T14:21:10ZCoordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration10.1038/s41536-021-00129-z2057-3995https://doaj.org/article/9fc6488438814df2a6871457cb867bcb2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00129-zhttps://doaj.org/toc/2057-3995Abstract Endogenous β cell regeneration could alleviate diabetes, but proliferative stimuli within the islet microenvironment are incompletely understood. We previously found that β cell recovery following hypervascularization-induced β cell loss involves interactions with endothelial cells (ECs) and macrophages (MΦs). Here we show that proliferative ECs modulate MΦ infiltration and phenotype during β cell loss, and recruited MΦs are essential for β cell recovery. Furthermore, VEGFR2 inactivation in quiescent ECs accelerates islet vascular regression during β cell recovery and leads to increased β cell proliferation without changes in MΦ phenotype or number. Transcriptome analysis of β cells, ECs, and MΦs reveals that β cell proliferation coincides with elevated expression of extracellular matrix remodeling molecules and growth factors likely driving activation of proliferative signaling pathways in β cells. Collectively, these findings suggest a new β cell regeneration paradigm whereby coordinated interactions between intra-islet MΦs, ECs, and extracellular matrix mediate β cell self-renewal.Diane C. SaundersKristie I. AamodtTiffany M. RichardsonAlexander J. HopkirkRadhika AramandlaGreg PoffenbergerRegina JenkinsDavid K. FlahertyNripesh PrasadShawn E. LevyAlvin C. PowersMarcela BrissovaNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Diane C. Saunders Kristie I. Aamodt Tiffany M. Richardson Alexander J. Hopkirk Radhika Aramandla Greg Poffenberger Regina Jenkins David K. Flaherty Nripesh Prasad Shawn E. Levy Alvin C. Powers Marcela Brissova Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration
description	Abstract Endogenous β cell regeneration could alleviate diabetes, but proliferative stimuli within the islet microenvironment are incompletely understood. We previously found that β cell recovery following hypervascularization-induced β cell loss involves interactions with endothelial cells (ECs) and macrophages (MΦs). Here we show that proliferative ECs modulate MΦ infiltration and phenotype during β cell loss, and recruited MΦs are essential for β cell recovery. Furthermore, VEGFR2 inactivation in quiescent ECs accelerates islet vascular regression during β cell recovery and leads to increased β cell proliferation without changes in MΦ phenotype or number. Transcriptome analysis of β cells, ECs, and MΦs reveals that β cell proliferation coincides with elevated expression of extracellular matrix remodeling molecules and growth factors likely driving activation of proliferative signaling pathways in β cells. Collectively, these findings suggest a new β cell regeneration paradigm whereby coordinated interactions between intra-islet MΦs, ECs, and extracellular matrix mediate β cell self-renewal.
format	article
author	Diane C. Saunders Kristie I. Aamodt Tiffany M. Richardson Alexander J. Hopkirk Radhika Aramandla Greg Poffenberger Regina Jenkins David K. Flaherty Nripesh Prasad Shawn E. Levy Alvin C. Powers Marcela Brissova
author_facet	Diane C. Saunders Kristie I. Aamodt Tiffany M. Richardson Alexander J. Hopkirk Radhika Aramandla Greg Poffenberger Regina Jenkins David K. Flaherty Nripesh Prasad Shawn E. Levy Alvin C. Powers Marcela Brissova
author_sort	Diane C. Saunders
title	Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration
title_short	Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration
title_full	Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration
title_fullStr	Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration
title_full_unstemmed	Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration
title_sort	coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9fc6488438814df2a6871457cb867bcb
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Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration

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