Abstract
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.
Highlights
Chronic kidney disease (CKD), regardless of the initial cause of the renal disease, is characterized by the progressive deterioration of kidney function, the relentless accumulation and deposition of extracellular matrix, and progressive tissue fibrosis
This study explored whether the H2 relaxin ameliorated renal fibrosis at the early stage of ureteral obstruction (UUO) by shifting macrophage polarization toward the M2 phenotype
We found that relaxin can downregulate the TLR4-NF-ΚB signaling pathway at all levels
Summary
Chronic kidney disease (CKD), regardless of the initial cause of the renal disease, is characterized by the progressive deterioration of kidney function, the relentless accumulation and deposition of extracellular matrix, and progressive tissue fibrosis. Renal fibrosis is a common feature of CKD, contributes prominently to the progressive loss of organ structure and function and leads to end-stage renal failure [2]. Macrophages (MΦ), which have diverse functions and phenotypic plasticity, have been recognized as key factors in renal fibrosis. M1 macrophages play a pro-inflammatory role, enhancing renal inflammation by secreting pathogenic mediators, resulting in renal fibrosis. M2 macrophages play an antiinflammatory role, suppressing renal inflammation by releasing anti-inflammatory mediators, such as interleukin (IL)-10, resulting in reduced renal fibrosis [3, 4, 5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
