Colony-stimulating factor-1 promotes kidney growth and repair via alteration of macrophage responses

Maliha A Alikhan, Christina V Jones, Timothy M Williams, Anthony G Beckhouse, Anne L Fletcher, Michelle M Kett, Samy Sakkal, Chrishan S Samuel, Robert G Ramsay, James A Deane, Christine A Wells, Melissa H Little, David A Hume, Sharon D Ricardo

Research output: Contribution to journalArticlepeer-review

106 Citations (Scopus)

Abstract

Colony-stimulating factor (CSF)-1 controls the survival, proliferation, and differentiation of macrophages, which are recognized as scavengers and agents of the innate and the acquired immune systems. Because of their plasticity, macrophages are endowed with many other essential roles during development and tissue homeostasis. We present evidence that CSF-1 plays an important trophic role in postnatal organ growth and kidney repair. Notably, the injection of CSF-1 postnatally enhanced kidney weight and volume and was associated with increased numbers of tissue macrophages. Moreover, CSF-1 promotes postnatal renal repair in mice after ischemia-reperfusion injury by recruiting and influencing macrophages toward a reparative state. CSF-1 treatment rapidly accelerated renal repair with tubular epithelial cell replacement, attenuation of interstitial fibrosis, and functional recovery. Analysis of macrophages from CSF-1-treated kidneys showed increased expression of insulin-like growth factor-1 and anti-inflammatory genes that are known CSF-1 targets. Taken together, these data suggest that CSF-1 is important in kidney growth and the promotion of endogenous repair and resolution of inflammatory injury.

Original languageEnglish
Pages (from-to)1243-56
Number of pages14
JournalThe American Journal of Pathology
Volume179
Issue number3
DOIs
Publication statusPublished - Sept 2011

Keywords

  • Acute Kidney Injury
  • Animals
  • Animals, Newborn
  • Body Weight
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Collagen
  • Gene Expression Profiling
  • Kidney
  • Macrophage Colony-Stimulating Factor
  • Macrophages
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Organ Size
  • Phenotype
  • Recovery of Function
  • Reperfusion Injury

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