Canonical Wnt Signaling Promotes Macrophage Proliferation During Kidney Fibrosis

Overview

Journal Kidney Dis (Basel)

Specialty Nephrology

Date 2018 Jul 13

PMID 29998124

Citations 13

Authors

Ye Feng

Yan Liang

Jiafa Ren

Chunsun Dai

Affiliations

Soon will be listed here.

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.

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