TY - JOUR
T1 - The signaling protein Wnt5a promotes TGF1-mediated macrophage polarization and kidney fibrosis by inducing the transcriptional regulators Yap/Taz
AU - Feng, Ye
AU - Liang, Yan
AU - Zhu, Xingwen
AU - Wang, Mingjie
AU - Gui, Yuan
AU - Lu, Qingmiao
AU - Gu, Mengru
AU - Xue, Xian
AU - Sun, Xiaoli
AU - He, Weichun
AU - Yang, Junwei
AU - Johnson, Randy L.
AU - Dai, Chunsun
N1 - Funding Information:
This work was supported by National Science Foundation of China Grants 81570611/H0503 and 81770675/H0503 and Science Foundation of Jiangsu Province Grant BK20140048 (to C. D.). The authors declare that they have no conflicts of interest with the contents of this article. This article contains Fig. S1. 1To whom correspondence should be addressed. Tel.: 86-25-52636077; E-mail: daichunsun@njmu.edu.cn.
Funding Information:
This work was supported by National Science Foundation of China Grants 81570611/H0503 and 81770675/H0503 and Science Foundation of Jiangsu Province Grant BK20140048 (to C. D.). The authors declare that they have no conflicts of interest with the contents of this article.
Publisher Copyright:
© 2018 Feng et al.
PY - 2018/12/14
Y1 - 2018/12/14
N2 - M2 macrophage polarization is known to underlie kidney fibrosis. We previously reported that most of the members of the Wnt family of signaling proteins are induced in fibrotic kidneys. Dysregulation of the signaling protein Wnt5a is associated with fibrosis, but little is known about the role of Wnt5a in regulating M2 macrophage activation that results in kidney fibrosis. Here, using murine Raw 264.7 cells and bone marrow– derived macrophages, we found that Wnt5a enhanced transforming growth factor 1 (TGF1)-induced macrophage M2 polarization as well as expression of the transcriptional regulators Yes-associated protein (Yap)/transcriptional coactivator with PDZ-binding motif (Taz). Verteporfin blockade of Yap/Taz inhibited both Wnt5a- and TGF1-induced macrophage M2 polarization. In mouse models of kidney fibrosis, shRNA-mediated knockdown of Wnt5a expression diminished kidney fibrosis, macrophage Yap/Taz expression, and M2 polarization. Moreover, genetic ablation of Taz in macrophages attenuated kidney fibrosis and macrophage M2 polarization in mice. Collectively, these results indicate that Wnt5a promotes kidney fibrosis by stimulating Yap/Taz-mediated macrophage M2 polarization.
AB - M2 macrophage polarization is known to underlie kidney fibrosis. We previously reported that most of the members of the Wnt family of signaling proteins are induced in fibrotic kidneys. Dysregulation of the signaling protein Wnt5a is associated with fibrosis, but little is known about the role of Wnt5a in regulating M2 macrophage activation that results in kidney fibrosis. Here, using murine Raw 264.7 cells and bone marrow– derived macrophages, we found that Wnt5a enhanced transforming growth factor 1 (TGF1)-induced macrophage M2 polarization as well as expression of the transcriptional regulators Yes-associated protein (Yap)/transcriptional coactivator with PDZ-binding motif (Taz). Verteporfin blockade of Yap/Taz inhibited both Wnt5a- and TGF1-induced macrophage M2 polarization. In mouse models of kidney fibrosis, shRNA-mediated knockdown of Wnt5a expression diminished kidney fibrosis, macrophage Yap/Taz expression, and M2 polarization. Moreover, genetic ablation of Taz in macrophages attenuated kidney fibrosis and macrophage M2 polarization in mice. Collectively, these results indicate that Wnt5a promotes kidney fibrosis by stimulating Yap/Taz-mediated macrophage M2 polarization.
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U2 - 10.1074/jbc.RA118.005457
DO - 10.1074/jbc.RA118.005457
M3 - Article
C2 - 30333225
AN - SCOPUS:85058571761
SN - 0021-9258
VL - 293
SP - 19290
EP - 19302
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 50
ER -