TGF-β promotes fibrosis after severe acute kidney injury by enhancing renal macrophage infiltration

被引：94

作者：

Chung, Sungjin ^{[1
,2
,3
]}

Overstreet, Jessica M. ^{[1
,2
]}

Li, Yan ^{[1
,2
]}

Wang, Yinqiu ^{[1
,2
]}

Niu, Aolei ^{[1
,2
]}

Wang, Suwan ^{[1
,2
]}

Fan, Xiaofeng ^{[1
,2
]}

Sasaki, Kensuke ^{[1
,2
]}

Jin, Guan-Nan ^{[1
,2
]}

Khodo, Stellor Nlandu ^{[1
,2
]}

Gewin, Leslie ^{[1
,2
]}

Zhang, Ming-Zhi ^{[1
,2
]}

Harris, Raymond C. ^{[1
,2
,4
]}

机构：

[1] Vanderbilt Univ, Sch Med, Div Nephrol & Hypertens, Dept Med, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Sch Med, Vanderbilt Ctr Kidney Dis, Nashville, TN 37232 USA

[3] Catholic Univ Korea, Coll Med, Dept Internal Med, Seoul, South Korea

[4] Dept Vet Affairs, Nashville, TN USA

来源：

JCI INSIGHT | 2018年 / 3卷 / 21期

关键词：

GROWTH-FACTOR RECEPTOR; ISCHEMIA-REPERFUSION; CELLS; CYCLOOXYGENASE-2; RECOVERY; POLARIZATION; NEPHROPATHY; INHIBITION; EXPRESSION; DELETION;

D O I：

10.1172/jci.insight.123563

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

TGF-beta signals through a receptor complex composed of 2 type I and 2 type II (TGF-beta RII) subunits. We investigated the role of macrophage TGF-ss signaling in fibrosis after AKI in mice with selective monocyte/macrophage TGF-beta RII deletion (macrophage TGF-beta RII(-/-)mice). Four weeks after injury, renal TGF-beta 1 expression and fibrosis were higher in WT mice than macrophage TGF-beta RII(-/-)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-beta RII(-/-)mice, but TGF-beta RII-/-BMMs did not respond to TGF-beta. We then implanted Matrigel plugs suffused with either f-Met-Leu-Phe or TGF-beta 1 into WT or macrophage TGF-beta RII(-/-)mice. After 6 days, f-Met-Leu-Phe induced similar macrophage infiltration into the Matrigel plugs of WT and macrophage TGF-beta RII(-/-)mice, but TGF-beta induced infiltration only in WT mice. We further determined the number of labeled WT or TGF-beta RII-/-BMMs infiltrating into WT kidneys 20 days after ischemic injury. There were more labeled WT BMMs than TGF-beta RII-/-BMMs. Therefore, macrophage TGF-beta RII deletion protects against the development of tubulointerstitial fibrosis following severe ischemic renal injury. Chemoattraction of macrophages to the injured kidney through a TGF-beta/TGF-beta RII axis is a heretofore undescribed mechanism by which TGF-beta can mediate renal fibrosis during progressive renal injury.

引用

页数：15

共 37 条

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