Wnt/β-Catenin-Promoted Macrophage Alternative Activation Contributes to Kidney Fibrosis.

Abstract

The Wnt/β-catenin pathway is crucial in normal development and throughout life, but aberrant activation of this pathway has been linked to kidney fibrosis, although the mechanisms involved remain incompletely determined. Here, we investigated the role of Wnt/β-catenin in regulating macrophage activation and the contribution thereof to kidney fibrosis. Treatment of macrophages with Wnt3a exacerbated IL-4- or TGFβ1-induced macrophage alternative (M2) polarization and the phosphorylation and nuclear translocation of STAT3 in vitro Conversely, inhibition of Wnt/β-catenin signaling prevented these IL-4- or TGFβ1-induced processes. In a mouse model, induced deletion of β-catenin in macrophages attenuated the fibrosis, macrophage accumulation, and M2 polarization observed in the kidneys of wild-type littermates after unilateral ureter obstruction. This study shows that activation of Wnt/β-catenin signaling promotes kidney fibrosis by stimulating macrophage M2 polarization.

• Authors: Ye Feng, Jiafa Ren, Yuan Gui, Wei Wei, Bingyan Shu, Qingmiao Lu, Xian Xue, Xiaoli Sun, Weichun He, Junwei Yang, Chunsun Dai
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 29 Issue 1 Pg. 182-193 (01 2018) ISSN: 1533-3450 [Electronic] United States
• PMID: 29021383 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 by the American Society of Nephrology.

Chemical References

• Il4 protein, mouse
• STAT3 Transcription Factor
• Stat3 protein, mouse
• Tgfb1 protein, mouse
• Transforming Growth Factor beta1
• Wnt3A Protein
• Wnt3a protein, mouse
• beta Catenin
• Interleukin-4

Topics

• Animals
• Biological Transport (drug effects)
• Cell Line
• Fibrosis
• Interleukin-4 (metabolism)
• Kidney (pathology)
• Macrophage Activation
• Macrophages (physiology)
• Male
• Mice
• Mice, Knockout
• Phosphorylation (drug effects)
• STAT3 Transcription Factor (metabolism)
• Transforming Growth Factor beta1 (metabolism)
• Ureteral Obstruction (complications)
• Wnt Signaling Pathway
• Wnt3A Protein (pharmacology)
• beta Catenin (genetics, metabolism)