Adipocytes upregulate endothelial miR-21 to promote angiogenesis and alleviate acute kidney injury.

Authors

Hengyuan Zhang, Xiuyuan Shi, Zilong Xu, Danling Wang, Zhikai Tan

Published in

Cellular signalling. Pages 112972. Oct 25, 2026. Epub Oct 25, 2026.

Abstract

Acute kidney injury (AKI) is a severe condition with high morbidity and mortality, often progressing to chronic kidney disease. During AKI progression, the regulation of hypoxic stress and promotion of angiogenesis are crucial. The role of systemic hypoxia in modulating renal repair remains incompletely understood. This study investigates how hypoxic adipocytes promote angiogenesis in early-stage AKI. Conditioned medium was collected from hypoxic adipocytes to simulate paracrine effects. Endothelial cell proliferation, migration, and tube formation were assessed using CCK-8, scratch wound, Transwell, and Matrigel assays. Expression of miR-21, SPRY1, and vascular endothelial growth factor (VEGF) was measured by qPCR and western blotting. In a mouse model of renal ischemia-reperfusion injury, conditioned medium was administered by injection. Renal injury, fibrosis, and peritubular capillary density were evaluated by histology and immunofluorescence. Conditioned medium from hypoxic adipocytes significantly enhanced endothelial cell proliferation, migration, and tube formation, accompanied by increased miR-21 and decreased SPRY1 expression. Mechanistically, miR-21 promoted angiogenesis by suppressing SPRY1 and activating the ERK/MAPK pathway. In vivo, conditioned medium restored peritubular capillary density, reduced fibrosis and tubular damage, and improved renal recovery following ischemia-reperfusion injury. The results indicate that hypoxic adipocytes promote vascular repair in AKI through a paracrine mechanism involving the upregulation of miR-21 in endothelial cells and activation of the SPRY1/ERK/MAPK axis. This pathway represents a promising therapeutic target for AKI.

PMID:
42927819
Bibliographic data and abstract were imported from PubMed on 26 Oct 2026.

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