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

Research output: Contribution to journalArticle

169 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4519-4532
Number of pages14
JournalJournal of Clinical Investigation
Volume122
Issue number12
DOIs
StatePublished - Dec 3 2012

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Macrophage Colony-Stimulating Factor
Acute Kidney Injury
Kidney
Macrophages
Dendritic Cells
Diphtheria Toxin
Regeneration
Wounds and Injuries
Reperfusion Injury
Wound Healing
Reperfusion
Monocytes
Ischemia
Epithelium
Cell Proliferation
Apoptosis
Phenotype

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Zhang, M. Z., Yao, B., Yang, S., Jiang, L., Wang, S., Fan, X., ... Harris, R. C. (2012). CSF-1 signaling mediates recovery from acute kidney injury. Journal of Clinical Investigation, 122(12), 4519-4532. https://doi.org/10.1172/JCI60363

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

In: Journal of Clinical Investigation, Vol. 122, No. 12, 03.12.2012, p. 4519-4532.

Research output: Contribution to journalArticle

Zhang, MZ, Yao, B, Yang, S, Jiang, L, Wang, S, Fan, X, Yin, H, Wong, K, Miyazawa, T, Chen, J, Chang, I, Singh, A & Harris, RC 2012, 'CSF-1 signaling mediates recovery from acute kidney injury', Journal of Clinical Investigation, vol. 122, no. 12, pp. 4519-4532. https://doi.org/10.1172/JCI60363
Zhang MZ, Yao B, Yang S, Jiang L, Wang S, Fan X et al. CSF-1 signaling mediates recovery from acute kidney injury. Journal of Clinical Investigation. 2012 Dec 3;122(12):4519-4532. https://doi.org/10.1172/JCI60363
Zhang, Ming Zhi ; Yao, Bing ; Yang, Shilin ; Jiang, Li ; Wang, Suwan ; Fan, Xiaofeng ; Yin, Huiyong ; Wong, Karlton ; Miyazawa, Tomoki ; Chen, Jianchun ; Chang, Ingrid ; Singh, Amar ; Harris, Raymond C. / CSF-1 signaling mediates recovery from acute kidney injury. In: Journal of Clinical Investigation. 2012 ; Vol. 122, No. 12. pp. 4519-4532.
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