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Proximal tubule-derived colony stimulating factor-1 mediates polarization of renal macrophages and dendritic cells, and recovery in acute kidney injury
- Source :
- Kidney international
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- Infiltrating cells play an important role in both the development of and recovery from acute kidney injury (AKI). Macrophages and renal dendritic cells are of particular interest because they can exhibit distinctly different functional phenotypes, broadly characterized as proinflammatory (M1) or tissue reparative (M2). Resident renal macrophages and dendritic cells participate in recovery from AKI in response to either ischemia/reperfusion or a model of selective proximal tubule injury induced by diphtheria-toxin-induced apoptosis in transgenic mice expressing the human diphtheria toxin receptor on proximal tubule cells. Colony-stimulating factor-1 (CSF-1) is an important factor mediating the recovery from AKI, and CSF-1 can stimulate macrophage and dendritic cell proliferation and polarization during the recovery phase of AKI. The kidney, and specifically the proximal tubule, is a major source of intrarenal CSF-1 production in response to AKI. We induced selective deletion of proximal tubule CSF-1 to determine its role in expansion and proliferation of renal macrophages and dendritic cells and in recovery from AKI. In both models of AKI, there was decreased M2 polarization, delayed functional and structural recovery, and increased tubulointerstitial fibrosis. Thus, intrarenal CSF-1 is an important mediator of macrophage/dendritic cell polarization and recovery from AKI.
- Subjects :
- Macrophage colony-stimulating factor
dendritic cell
030232 urology & nephrology
macrophage
Biology
urologic and male genital diseases
Article
c-fms
Proinflammatory cytokine
Dendritic cell proliferation
03 medical and health sciences
AKI
0302 clinical medicine
CSF-1
proximal tubule
diphtheria toxin
medicine
030304 developmental biology
0303 health sciences
Kidney
Acute kidney injury
Dendritic cell
medicine.disease
female genital diseases and pregnancy complications
medicine.anatomical_structure
Nephrology
Apoptosis
Immunology
Cancer research
Tubulointerstitial fibrosis
Subjects
Details
- ISSN :
- 00852538
- Volume :
- 88
- Database :
- OpenAIRE
- Journal :
- Kidney International
- Accession number :
- edsair.doi.dedup.....06e6a19c8129b65455d9e2dd18253f84