Perivascular CD73+ cells attenuate inflammation and interstitial fibrosis in the kidney microenvironment.
Am J Physiol Renal Physiol
; 317(3): F658-F669, 2019 09 01.
Article
em En
| MEDLINE
| ID: mdl-31364375
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-ß 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
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5'-Nucleotidase
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Pericitos
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Microambiente Celular
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Fibroblastos
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Rim
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Macrófagos
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Nefrite Intersticial
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Am J Physiol Renal Physiol
Ano de publicação:
2019
Tipo de documento:
Article