CSF-1 signaling mediates recovery from acute kidney injury
Ming-Zhi Zhang, Bing Yao, Shilin Yang, Li Jiang, Suwan Wang, Xiaofeng Fan, Huiyong Yin, Karlton Wong, Tomoki Miyazawa, Jianchun Chen, Ingrid Chang, Amar Singh, Raymond C. Harris
Ming-Zhi Zhang, Bing Yao, Shilin Yang, Li Jiang, Suwan Wang, Xiaofeng Fan, Huiyong Yin, Karlton Wong, Tomoki Miyazawa, Jianchun Chen, Ingrid Chang, Amar Singh, Raymond C. Harris
View: Text | PDF
Research Article Nephrology

CSF-1 signaling mediates recovery from acute kidney injury

Abstract

Renal tubule epithelia represent the primary site of damage in acute kidney injury (AKI), a process initiated and propagated by the infiltration of macrophages. Here we investigated the role of resident renal macrophages and dendritic cells in recovery from AKI after ischemia/reperfusion (I/R) injury or a novel diphtheria toxin–induced (DT-induced) model of selective proximal tubule injury in mice. DT-induced AKI was characterized by marked renal proximal tubular cell apoptosis. In both models, macrophage/dendritic cell depletion during the recovery phase increased functional and histologic injury and delayed regeneration. After I/R-induced AKI, there was an early increase in renal macrophages derived from circulating inflammatory (M1) monocytes, followed by accumulation of renal macrophages/dendritic cells with a wound-healing (M2) phenotype. In contrast, DT-induced AKI only generated an increase in M2 cells. In both models, increases in M2 cells resulted largely from in situ proliferation in the kidney. Genetic or pharmacologic inhibition of macrophage colony-stimulating factor (CSF-1) signaling blocked macrophage/dendritic cell proliferation, decreased M2 polarization, and inhibited recovery. These findings demonstrated that CSF-1–mediated expansion and polarization of resident renal macrophages/dendritic cells is an important mechanism mediating renal tubule epithelial regeneration after AKI.

Authors

Ming-Zhi Zhang, Bing Yao, Shilin Yang, Li Jiang, Suwan Wang, Xiaofeng Fan, Huiyong Yin, Karlton Wong, Tomoki Miyazawa, Jianchun Chen, Ingrid Chang, Amar Singh, Raymond C. Harris

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (703.25 KB)

Advertisement