Macrophage Wnt7b is critical for kidney repair and regeneration

Shuei Liong Lin, Bing Li, Sujata Rao, Eun Jin Yeo, Thomas E. Hudson, Brian T. Nowlin, Huaying Pei, Lijun Chen, Jie J. Zheng, Thomas J. Carroll, Jeffrey W. Pollard, Andrew P. McMahon, Richard A. Lang, Jeremy S. Duffield

Research output: Contribution to journalArticle

269 Scopus citations

Abstract

Macrophages are required for tissue homeostasis through their role in regulation of the immune response and the resolution of injury. Here we show, using the kidney as a model, that the Wnt pathway ligand Wnt7b is produced by macrophages to stimulate repair and regeneration. When macrophages are inducibly ablated from the injured kidney, the canonical Wnt pathway response in kidney epithelial cells is reduced. Furthermore, when Wnt7b is somatically deleted in macrophages, repair of injury is greatly diminished. Finally, injection of the Wnt pathway regulator Dkk2 enhances the repair process and suggests a therapeutic option. Because Wnt7b is known to stimulate epithelial responses during kidney development, these findings suggest that macrophages are able to rapidly invade an injured tissue and reestablish a developmental program that is beneficial for repair and regeneration.

Original languageEnglish (US)
Pages (from-to)4194-4199
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number9
DOIs
StatePublished - Mar 2 2010

Keywords

  • Canonical Wnt pathway
  • Kidney
  • Macrophage
  • Regeneration
  • Repair

ASJC Scopus subject areas

  • General

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  • Cite this

    Lin, S. L., Li, B., Rao, S., Yeo, E. J., Hudson, T. E., Nowlin, B. T., Pei, H., Chen, L., Zheng, J. J., Carroll, T. J., Pollard, J. W., McMahon, A. P., Lang, R. A., & Duffield, J. S. (2010). Macrophage Wnt7b is critical for kidney repair and regeneration. Proceedings of the National Academy of Sciences of the United States of America, 107(9), 4194-4199. https://doi.org/10.1073/pnas.0912228107