Macrophage Wnt7b is critical for kidney repair and regeneration.
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.
Laboratory of Inflammation Research, Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Shuei-Liong
SL
Lin
Bing
B
Li
Sujata
S
Rao
Eun-Jin
EJ
Yeo
Thomas E
TE
Hudson
Brian T
BT
Nowlin
Huaying
H
Pei
Lijun
L
Chen
Jie J
JJ
Zheng
Thomas J
TJ
Carroll
Jeffrey W
JW
Pollard
Andrew P
AP
McMahon
Richard A
RA
Lang
Jeremy S
JS
Duffield
D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D012038:Regeneration; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism / Q000502:physiology*
D017931:DNA Primers; C405060:Dkk2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C095937:Wnt7b protein, mouse