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http://ir.nhri.org.tw/handle/3990099045/11899
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| Title: | Compound K inhibits priming and mitochondria-associated activating signals of NLRP3 inflammasome in renal tubulointerstitial lesions |
| Authors: | Hsu, WH;Hua, KF;Tuan, LH;Tsai, YL;Chu, LJ;Lee, YC;Wong, WT;Lee, SL;Lai, JH;Chu, CL;Ho, LJ;Chiu, HW;Hsu, YJ;Chen, CH;Ka, SM;Chen, A |
| Contributors: | Institute of Cellular and Systems Medicine |
| Abstract: | BACKGROUND: Renal tubulointerstitial lesions (TILs), a key pathological hallmark for chronic kidney disease to progress to end-stage renal disease, feature renal tubular atrophy, interstitial mononuclear leukocyte infiltration and fibrosis in the kidney. Our study tested the renoprotective and therapeutic effects of compound K (CK), as described in our US patent (US7932057B2), on renal TILs using a mouse unilateral ureteral obstruction (UUO) model. METHODS: Renal pathology was performed and renal draining lymph nodes were subjected to flow cytometry analysis. Mechanism-based experiments included the analysis of mitochondrial dysfunction, a model of tubular epithelial cells (TECs) under mechanically induced constant pressure (MICP) and tandem mass tags (TMT)-based proteomics analysis. RESULTS: Administration of CK ameliorated renal TILs by reducing urine levels of proinflammatory cytokines, and preventing mononuclear leukocyte infiltration and fibrosis in the kidney. The beneficial effects clearly correlated with its inhibition of: (i) NF-kappaB-associated priming and the mitochondria-associated activating signals of the NLRP3 inflammasome; (ii) STAT3 signalling, which in part prevents NLRP3 inflammasome activation; and (iii) the TGF-beta-dependent Smad2/Smad3 fibrotic pathway, in renal tissues, renal TECs under MICP and/or activated macrophages, the latter as a major inflammatory player contributing to renal TILs. Meanwhile, TMT-based proteomics analysis revealed downregulated renal NLRP3 inflammasome activation-associated signalling pathways in CK-treated UUO mice. CONCLUSIONS: The present study, for the first time, presents the potent renoprotective and therapeutic effects of CK on renal TILs by targeting the NLRP3 inflammasome and STAT3 signalling. |
| Date: | 2020-01 |
| Relation: | Nephrology, Cialysis, Transplantation. 2020 Jan;35(1):74-85. |
| Link to: | http://dx.doi.org/10.1093/ndt/gfz073 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0931-0509&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000518533600010 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85077953126 |
| Appears in Collections: | [何令君] 期刊論文
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| PUB31065699.pdf | | 2166Kb | Adobe PDF | 283 | View/Open |
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