| Literature DB >> 30385721 |
Sungjin Chung1,2,3, Jessica M Overstreet1,2, Yan Li1,2, Yinqiu Wang1,2, Aolei Niu1,2, Suwan Wang1,2, Xiaofeng Fan1,2, Kensuke Sasaki1,2, Guan-Nan Jin1,2, Stellor Nlandu Khodo1,2, Leslie Gewin1,2, Ming-Zhi Zhang1,2, Raymond C Harris1,2,4.
Abstract
TGF-β signals through a receptor complex composed of 2 type I and 2 type II (TGF-βRII) subunits. We investigated the role of macrophage TGF-β signaling in fibrosis after AKI in mice with selective monocyte/macrophage TGF-βRII deletion (macrophage TGF-βRII-/- mice). Four weeks after injury, renal TGF-β1 expression and fibrosis were higher in WT mice than macrophage TGF-βRII-/- mice, which had decreased renal macrophages. The in vitro chemotactic response to f-Met-Leu-Phe was comparable between bone marrow-derived monocytes (BMMs) from WT and macrophage TGF-βRII-/- mice, but TGF-βRII-/- BMMs did not respond to TGF-β. We then implanted Matrigel plugs suffused with either f-Met-Leu-Phe or TGF-β1 into WT or macrophage TGF-βRII-/- mice. After 6 days, f-Met-Leu-Phe induced similar macrophage infiltration into the Matrigel plugs of WT and macrophage TGF-βRII-/- mice, but TGF-β induced infiltration only in WT mice. We further determined the number of labeled WT or TGF-βRII-/- BMMs infiltrating into WT kidneys 20 days after ischemic injury. There were more labeled WT BMMs than TGF-βRII-/- BMMs. Therefore, macrophage TGF-βRII deletion protects against the development of tubulointerstitial fibrosis following severe ischemic renal injury. Chemoattraction of macrophages to the injured kidney through a TGF-β/TGF-βRII axis is a heretofore undescribed mechanism by which TGF-β can mediate renal fibrosis during progressive renal injury.Entities:
Keywords: Chemokines; Fibrosis; Macrophages; Nephrology
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Year: 2018 PMID： 30385721 PMCID： PMC6238749 DOI： 10.1172/jci.insight.123563
Source DB: PubMed Journal: JCI Insight ISSN： 2379-3708