Perivascular CD73+ cells attenuate inflammation and interstitial fibrosis in the kidney microenvironment

American Journal of Physiology. Renal Physiology
Heather M PerryMark D Okusa

Abstract

Progressive tubulointerstitial fibrosis may occur after acute kidney injury due to persistent inflammation. Purinergic signaling by 5'-ectonucleotidase, CD73, an enzyme that converts AMP to adenosine on the extracellular surface, can suppress inflammation. The role of CD73 in progressive kidney fibrosis has not been elucidated. We evaluated the effect of deletion of CD73 from kidney perivascular cells (including pericytes and/or fibroblasts of the Foxd1+ lineage) on fibrosis. Perivascular cell expression of CD73 was necessary to suppress inflammation and prevent kidney fibrosis in Foxd1CreCD73fl/fl mice evaluated 14 days after unilateral ischemia-reperfusion injury or folic acid treatment (250 mg/kg). Kidneys of Foxd1CreCD73fl/fl mice had greater collagen deposition, expression of proinflammatory markers (including various macrophage markers), and platelet-derived growth factor recepetor-β immunoreactivity than CD73fl/fl mice. Kidney dysfunction and fibrosis were rescued by administration of soluble CD73 or by macrophage deletion. Isolated CD73-/- kidney pericytes displayed an activated phenotype (increased proliferation and α-smooth muscle actin mRNA expression) compared with wild-type controls. In conclusion, CD73 in perivasc...Continue Reading

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Citations

Aug 14, 2020·Proceedings of the National Academy of Sciences of the United States of America·Patrick Ming-Kuen TangHui-Yao Lan
Dec 20, 2020·Biochemical Pharmacology·Gennady G Yegutkin
Jun 2, 2021·ACR Open Rheumatology·Anne Davidson

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Methods Mentioned

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polarized microscopy
PCR
flow cytometry

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ImageJ
GraphPad
Prism
StereoInvestigator
FlowJo

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