Department of Internal Medicine, Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Internal Medicine, Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
J Am Soc Nephrol. 2018 Jan;29(1):182-193. doi: 10.1681/ASN.2017040391. Epub 2017 Oct 11.
The Wnt/-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/-catenin in regulating macrophage activation and the contribution thereof to kidney fibrosis. Treatment of macrophages with Wnt3a exacerbated IL-4- or TGF1-induced macrophage alternative (M2) polarization and the phosphorylation and nuclear translocation of STAT3 Conversely, inhibition of Wnt/-catenin signaling prevented these IL-4- or TGF1-induced processes. In a mouse model, induced deletion of -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/-catenin signaling promotes kidney fibrosis by stimulating macrophage M2 polarization.
Wnt/-catenin 通路在正常发育和整个生命周期中都至关重要，但该通路的异常激活已与肾脏纤维化有关，尽管涉及的机制仍不完全确定。在这里，我们研究了 Wnt/-catenin 在调节巨噬细胞激活及其对肾脏纤维化的贡献中的作用。用 Wnt3a 处理巨噬细胞会加剧 IL-4 或 TGF1 诱导的巨噬细胞替代（M2）极化，以及 STAT3 的磷酸化和核转位。相反，抑制 Wnt/-catenin 信号会阻止这些 IL-4 或 TGF1 诱导的过程。在小鼠模型中，诱导性地在巨噬细胞中缺失 -catenin 可减轻单侧输尿管梗阻后野生型同窝仔鼠肾脏中观察到的纤维化、巨噬细胞积聚和 M2 极化。这项研究表明，Wnt/-catenin 信号的激活通过刺激巨噬细胞 M2 极化促进肾脏纤维化。
