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

Heather M. Perry, Nicole Görldt, Sun Sang J. Sung, Liping Huang, Kinga P. Rudnicka, Iain M. Encarnacion, Amandeep Bajwa, Shinji Tanaka, Nabin Poudel, Junlan Yao, Diane L. Rosin, Jürgen Schrader, Mark D. Okusa

Research output: Contribution to journalArticle

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 perivascular cells may act to suppress myofibroblast transformation and influence macrophages to promote a wound healing response. These results suggest that the purinergic signaling pathway in the kidney interstitial microenvironment orchestrates perivascular cells and macrophages to suppress inflammation and prevent progressive fibrosis.

Original languageEnglish (US)
Pages (from-to)F658-F669
JournalAmerican journal of physiology. Renal physiology
Volume317
Issue number3
DOIs
StatePublished - Sep 1 2019

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Fibrosis
Inflammation
Kidney
Macrophages
Pericytes
Myofibroblasts
Platelet-Derived Growth Factor
Adenosine Monophosphate
Reperfusion Injury
Folic Acid
Acute Kidney Injury
Adenosine
Wound Healing
Smooth Muscle
Actins
Collagen
Fibroblasts
Phenotype
Messenger RNA
Enzymes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Perry, H. M., Görldt, N., Sung, S. S. J., Huang, L., Rudnicka, K. P., Encarnacion, I. M., ... Okusa, M. D. (2019). Perivascular CD73+ cells attenuate inflammation and interstitial fibrosis in the kidney microenvironment. American journal of physiology. Renal physiology, 317(3), F658-F669. https://doi.org/10.1152/ajprenal.00243.2019

Perivascular CD73+ cells attenuate inflammation and interstitial fibrosis in the kidney microenvironment. / Perry, Heather M.; Görldt, Nicole; Sung, Sun Sang J.; Huang, Liping; Rudnicka, Kinga P.; Encarnacion, Iain M.; Bajwa, Amandeep; Tanaka, Shinji; Poudel, Nabin; Yao, Junlan; Rosin, Diane L.; Schrader, Jürgen; Okusa, Mark D.

In: American journal of physiology. Renal physiology, Vol. 317, No. 3, 01.09.2019, p. F658-F669.

Research output: Contribution to journalArticle

Perry, HM, Görldt, N, Sung, SSJ, Huang, L, Rudnicka, KP, Encarnacion, IM, Bajwa, A, Tanaka, S, Poudel, N, Yao, J, Rosin, DL, Schrader, J & Okusa, MD 2019, 'Perivascular CD73+ cells attenuate inflammation and interstitial fibrosis in the kidney microenvironment', American journal of physiology. Renal physiology, vol. 317, no. 3, pp. F658-F669. https://doi.org/10.1152/ajprenal.00243.2019
Perry, Heather M. ; Görldt, Nicole ; Sung, Sun Sang J. ; Huang, Liping ; Rudnicka, Kinga P. ; Encarnacion, Iain M. ; Bajwa, Amandeep ; Tanaka, Shinji ; Poudel, Nabin ; Yao, Junlan ; Rosin, Diane L. ; Schrader, Jürgen ; Okusa, Mark D. / Perivascular CD73+ cells attenuate inflammation and interstitial fibrosis in the kidney microenvironment. In: American journal of physiology. Renal physiology. 2019 ; Vol. 317, No. 3. pp. F658-F669.
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