Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
TGF-β promotes fibrosis after severe acute kidney injury by enhancing renal macrophage infiltration
Sungjin Chung, … , Ming-Zhi Zhang, Raymond C. Harris
Sungjin Chung, … , Ming-Zhi Zhang, Raymond C. Harris
Published November 2, 2018
Citation Information: JCI Insight. 2018;3(21):e123563. https://doi.org/10.1172/jci.insight.123563.
View: Text | PDF
Research Article Nephrology

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

  • Text
  • PDF
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.

Authors

Sungjin Chung, Jessica M. Overstreet, Yan Li, Yinqiu Wang, Aolei Niu, Suwan Wang, Xiaofeng Fan, Kensuke Sasaki, Guan-Nan Jin, Stellor Nlandu Khodo, Leslie Gewin, Ming-Zhi Zhang, Raymond C. Harris

×

Full Text PDF | Download (70.11 MB)


Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts