Open AccessPersistent expression of neutrophil gelatinase‐associated lipocalin and M2 macrophage markers and chronic fibrosis after acute kidney injury
Author(s) -
Saito Hisako,
Tanaka Tetsuhiro,
Tanaka Shinji,
Higashijima Yoshiki,
Yamaguchi Junna,
Sugahara Mai,
Ito Marie,
Uchida Lisa,
Hasegawa Sho,
Wakashima Takeshi,
Fukui Kenji,
Nangaku Masaomi
Publication year - 2018
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13707
Subject(s) - fibrosis , medicine , lipocalin , acute kidney injury , kidney disease , ccr2 , kidney , creatinine , pathology , inflammation , chemokine , immunology , endocrinology , chemokine receptor
Recent epidemiologic studies revealed a correlation between acute kidney injury ( AKI ) episodes and the progression to chronic kidney disease ( CKD ). Although the severity and duration of the initial insult likely predict the development of CKD , information regarding tissue markers predictive of early development of renal fibrosis is limited. We investigated key markers in fibrotic kidney in rats and mice. Seven‐ to eight‐week‐old male Sprague–Dawley rats underwent bilateral ischemia–reperfusion injury ( IRI ). Kidney tissues were collected to determine the markers correlated with the severity of kidney fibrosis. In a separate set, a specific chemokine (C‐C motif) receptor 2 ( CCR 2) inhibitor, RS ‐102895, was administered to 9‐week‐old male C57 BL /6J mice that underwent unilateral IRI (9.2 mg/kg/day in drinking water for 17 days) to investigate whether blockade of the monocyte chemotactic protein‐1 ( MCP ‐1) signaling was sufficient to prevent fibrosis. Among candidate tissue markers, neutrophil gelatinase‐associated lipocalin ( NGAL ) and MCP ‐1 mRNA expressions were correlated with kidney fibrosis. Studies on macrophage polarity showed that mRNA expression of M2, but not M1 macrophage markers, were correlated with acute‐phase serum creatinine and fibrosis. Pharmacological blockade of the MCP ‐1– CCR 2 signaling downregulated CCR 2, which was insufficient to improve fibrosis in mouse unilateral IRI model, suggesting that additional, redundant pathways contribute to fibrosis. These findings suggested that tissue NGAL expression and M2 macrophage markers are promising markers that show severity of kidney fibrosis. Mechanistic involvement of these markers in CKD pathogenesis warrant additional investigation.