Relaxin abrogates renal interstitial fibrosis by regulating macrophage polarization via inhibition of Toll-like receptor 4 signaling
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Lei Chen1,*, Ming-Lei Sha2,*, Deng Li1,*, Yi-Ping Zhu1, Xing-Jie Wang1, Chen-Yi Jiang1, Shu-Jie Xia1, Yi Shao1
1Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2Department of Geriatric, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
*These authors are contributed equally to this work
Yi Shao, email: [email protected]
Keywords: renal fibrosis, relaxin, Toll-like receptor 4, macrophage polarization
Received: November 08, 2016 Accepted: February 07, 2017 Published: February 18, 2017
Renal fibrosis is a common feature of chronic kidney disease (CKD). To inhibit the CKD process, it is important to prevent renal fibrosis, though CKD remains incurable. Renal fibrosis can be inhibited by relaxin in several experimental models, but the mechanism of relaxin for antifibrotic potential is still not clear. And here we have studied the role of relaxin in macrophage polarization and renal inflammation after unilateral ureteral obstruction (UUO). Our results show that relaxin can downregulate the Toll-like receptor (TLR) 4 signaling, shift macrophage polarization toward the M2 phenotype and ameliorat renal fibrosis in the early stages of UUO. In vitro experiments, it has been confirmed that relaxin can downregulate the TLR4 signaling and induce the M2 macrophage transition. Furthermore, the transitional actions of macrophage phenotype induced by relaxin are significantly blocked by TAK-242, a TLR4 antagonist, in vitro experiments. Thus, there is a novel mechanism of relaxin for antifibrosis that shifts macrophage polarization toward the M2 phenotype via inhibition of TLR4 signaling.
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