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TGF-β promotes fibrosis after severe acute kidney injury by enhancing renal macrophage infiltration
- Source :
- JCI Insight. 3
- Publication Year :
- 2018
- Publisher :
- American Society for Clinical Investigation, 2018.
-
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.
- Subjects :
- Male
0301 basic medicine
Receptor complex
030232 urology & nephrology
Bone Marrow Cells
Mice, Transgenic
Kidney
Monocytes
Transforming Growth Factor beta1
Mice
03 medical and health sciences
0302 clinical medicine
Transforming Growth Factor beta
Fibrosis
Renal fibrosis
medicine
Animals
Matrigel
Chemotactic Factors
Chemistry
Macrophages
Monocyte
Receptor, Transforming Growth Factor-beta Type II
Acute kidney injury
General Medicine
Acute Kidney Injury
medicine.disease
Molecular biology
N-Formylmethionine Leucyl-Phenylalanine
030104 developmental biology
medicine.anatomical_structure
Tubulointerstitial fibrosis
Receptors, Transforming Growth Factor beta
Research Article
Subjects
Details
- ISSN :
- 23793708
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- JCI Insight
- Accession number :
- edsair.doi.dedup.....1d16a39b63a4a90e15a93bc7a7fd7eee