Renal Protection by Genetic Deletion of the Atypical Chemokine Receptor ACKR2 in Diabetic OVE Mice.

Journal of Diabetes Research
Shirong ZhengPaul N Epstein

Abstract

In diabetic nephropathy (DN) proinflammatory chemokines and leukocyte infiltration correlate with tubulointerstitial injury and declining renal function. The atypical chemokine receptor ACKR2 is a chemokine scavenger receptor which binds and sequesters many inflammatory CC chemokines but does not transduce typical G-protein mediated signaling events. ACKR2 is known to regulate diverse inflammatory diseases but its role in DN has not been tested. In this study, we utilized ACKR2(-/-) mice to test whether ACKR2 elimination alters progression of diabetic kidney disease. Elimination of ACKR2 greatly reduced DN in OVE26 mice, an established DN model. Albuminuria was significantly lower at 2, 4, and 6 months of age. ACKR2 deletion did not affect diabetic blood glucose levels but significantly decreased parameters of renal inflammation including leukocyte infiltration and fibrosis. Activation of pathways that increase inflammatory gene expression was attenuated. Human biopsies stained with ACKR2 antibody revealed increased staining in diabetic kidney, especially in some tubule and interstitial cells. The results demonstrate a significant interaction between diabetes and ACKR2 protein in the kidney. Unexpectedly, ACKR2 deletion reduced...Continue Reading

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Citations

Jul 5, 2016·Frontiers in Immunology·Raffaella Bonecchi, Gerard J Graham
Mar 7, 2020·Journal of Zhejiang University. Science. B·Zhi-Feng ZhouJin-Lei Lv
Sep 21, 2017·Journal of Diabetes Research·Yu YangJun-Kai Duan
Jul 29, 2020·International Urology and Nephrology·Gianluigi TavernaFabio Grizzi
May 6, 2020·International Journal of Molecular Sciences·Ting-Ting Chang, Jaw-Wen Chen
Nov 19, 2018·The American Journal of Pathology·Moritz LuxVolker Vielhauer
Nov 18, 2021··Paul Epstein, Shirong Zheng

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Datasets Mentioned

BETA
GSE51205

Methods Mentioned

BETA
ELISA
PCR
biopsies
transgenic

Software Mentioned

Adobe Photoshop
Ingenuity
Command Console
Ingenuity Pathway Analysis ( IPA )

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