Wnt/β-Catenin-Promoted Macrophage Alternative Activation Contributes to Kidney Fibrosis
Wnt/β-Catenin-Promoted Macrophage Alternative Activation Contributes to Kidney Fibrosis
复制标题
Wnt/β-连环蛋白促进巨噬细胞替代激活导致肾纤维化
DOI：
10.1681/asn.2017040391
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发表时间：
2018-01-01
影响因子：
13.6
通讯作者：
Dai, Chunsun
中科院分区：
文献类型：
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作者：
Feng, Ye;Ren, Jiafa;Dai, Chunsun
Wnt/β-连环蛋白通路在正常发育和整个生命过程中至关重要，但该通路的异常激活已与肾纤维化有关，尽管所涉及的机制尚未完全确定。在这里，我们研究了Wnt/β-连环蛋白在调节巨噬细胞活化中的作用及其对肾纤维化的贡献。在体外，用 Wnt3a 处理巨噬细胞会加剧 IL-4 或 TGF beta 1 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/β-连环蛋白信号传导可阻止这些 IL-4 或 TGF β 1 诱导的过程。在小鼠模型中，巨噬细胞中β-连环蛋白的诱导缺失减轻了单侧输尿管梗阻后野生型同窝小鼠肾脏中观察到的纤维化、巨噬细胞积累和 M2 极化。这项研究表明，Wnt/β-连环蛋白信号传导的激活通过刺激巨噬细胞 M2 极化来促进肾脏纤维化。
The Wnt/beta-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 ofWnt/beta-catenin in regulatingmacrophage activation and the contribution thereof to kidney fibrosis. Treatment of macrophages with Wnt3a exacerbated IL-4- or TGF beta 1-induced macrophage alternative (M2) polarization and the phosphorylation and nuclear translocation of STAT3 in vitro. Conversely, inhibition of Wnt/beta-catenin signaling prevented these IL-4- or TGF beta 1-induced processes. In a mouse model, induced deletion of beta-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/beta-catenin signaling promotes kidney fibrosis by stimulating macrophage M2 polarization.