Proximal tubule-derived colony stimulating factor-1 mediates polarization of renal macrophages and dendritic cells, and recovery in acute kidney injury

Yinqiu Wang, Jian Chang, Bing Yao, Aolei Niu, Emily Kelly, Matthew C. Breeggemann, Sherry L. Abboud Werner, Raymond C. Harris, Ming Zhi Zhang

Research output: Contribution to journalArticle

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1274-1282
Number of pages9
JournalKidney international
Volume88
Issue number6
DOIs
StatePublished - Dec 1 2015

Keywords

  • AKI
  • C-fms
  • CSF-1
  • Dendritic cell
  • Diphtheria toxin
  • Macrophage
  • Proximal tubule

ASJC Scopus subject areas

  • Nephrology

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    Wang, Y., Chang, J., Yao, B., Niu, A., Kelly, E., Breeggemann, M. C., Abboud Werner, S. L., Harris, R. C., & Zhang, M. Z. (2015). Proximal tubule-derived colony stimulating factor-1 mediates polarization of renal macrophages and dendritic cells, and recovery in acute kidney injury. Kidney international, 88(6), 1274-1282. https://doi.org/10.1038/ki.2015.295