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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) 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.

SUBMITTER: Saunders DC

PROVIDER: S-EPMC8024255 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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

Saunders Diane C DC Aamodt Kristie I KI Richardson Tiffany M TM Hopkirk Alexander J AJ Aramandla Radhika R Poffenberger Greg G Jenkins Regina R Flaherty David K DK Prasad Nripesh N Levy Shawn E SE Powers Alvin C AC Brissova Marcela M

NPJ Regenerative medicine 20210406 1

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 quie ...[more]

PMID: 33824346

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

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

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