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Macrophage Wnt7b is critical for kidney repair and regeneration.


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.

SUBMITTER: Lin SL 

PROVIDER: S-EPMC2840080 | biostudies-other | 2010 Mar

REPOSITORIES: biostudies-other

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Macrophage Wnt7b is critical for kidney repair and regeneration.

Lin Shuei-Liong SL   Li Bing B   Rao Sujata S   Yeo Eun-Jin EJ   Hudson Thomas E TE   Nowlin Brian T BT   Pei Huaying H   Chen Lijun L   Zheng Jie J JJ   Carroll Thomas J TJ   Pollard Jeffrey W JW   McMahon Andrew P AP   Lang Richard A RA   Duffield Jeremy S JS  

Proceedings of the National Academy of Sciences of the United States of America 20100216 9


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 gre  ...[more]

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