Ye Feng1, Yan Liang1, Jiafa Ren1, Chunsun Dai1. 1. Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract
BACKGROUND: Wnt/β-catenin, an evolutionary conserved signaling pathway, plays an essential role in modulating kidney injury and repair. Our previous studies demonstrated that Wnt/β-catenin signaling could stimulate macrophage M2 polarization and contribute to kidney fibrosis. However, whether canonical Wnt signaling activation leads to macrophage proliferation during kidney fibrosis remains to be determined. METHODS: In this study, a mouse model with macrophage-specific β-catenin gene deletion was generated and a unilateral ureter obstruction (UUO) model was created. RESULTS: In a mouse model with UUO nephropathy, deletion of β-catenin in macrophages attenuated macrophage proliferation and accumulation in kidney tissue. Wnt3a, a well-known canonical Wnt signaling stimulator, could markedly promote macrophage proliferation, whereas blocking canonical Wnt signaling with ICG-001 or ablating β-catenin could largely inhibit macrophage colony-stimulating factor-stimulated macrophage proliferation. Wnt3a treatment could time-dependently upregulate cyclin D1 protein expression and blocking β-catenin signaling could downregulate it. CONCLUSION: These results demonstrate that Wnt/ β-catenin signaling is essential for promoting macrophage proliferation during kidney fibrosis.
BACKGROUND: Wnt/β-catenin, an evolutionary conserved signaling pathway, plays an essential role in modulating kidney injury and repair. Our previous studies demonstrated that Wnt/β-catenin signaling could stimulate macrophage M2 polarization and contribute to kidney fibrosis. However, whether canonical Wnt signaling activation leads to macrophage proliferation during kidney fibrosis remains to be determined. METHODS: In this study, a mouse model with macrophage-specific β-catenin gene deletion was generated and a unilateral ureter obstruction (UUO) model was created. RESULTS: In a mouse model with UUO nephropathy, deletion of β-catenin in macrophages attenuated macrophage proliferation and accumulation in kidney tissue. Wnt3a, a well-known canonical Wnt signaling stimulator, could markedly promote macrophage proliferation, whereas blocking canonical Wnt signaling with ICG-001 or ablating β-catenin could largely inhibit macrophage colony-stimulating factor-stimulated macrophage proliferation. Wnt3a treatment could time-dependently upregulate cyclin D1 protein expression and blocking β-catenin signaling could downregulate it. CONCLUSION: These results demonstrate that Wnt/ β-catenin signaling is essential for promoting macrophage proliferation during kidney fibrosis.
Authors: Robert M Anthony; Joseph F Urban; Farhang Alem; Hossein A Hamed; Cristina T Rozo; Jean-Luc Boucher; Nico Van Rooijen; William C Gause Journal: Nat Med Date: 2006-07-30 Impact factor: 53.440
Authors: Bonnie E Jacques; Chandrakala Puligilla; Rachel M Weichert; Anna Ferrer-Vaquer; Anna-Katerina Hadjantonakis; Matthew W Kelley; Alain Dabdoub Journal: Development Date: 2012-12-01 Impact factor: 6.868