Protectin D1 inhibits TLR4 signaling pathway to alleviate non-alcoholic steatohepatitis via upregulating IRAK-M

作者全名："Liu, Hao; Li, Nana; Kuang, Ge; Gong, Xia; Wang, Ting; Hu, Jun; Du, Hui; Zhong, Minxuan; Guo, Jiashi; Xie, Yao; Xiang, Yang; Wu, Shengwang; Yuan, Yiling; Yin, Xinru; Wan, Jingyuan; Li, Ke"

作者地址："[Liu, Hao; Li, Nana; Kuang, Ge; Hu, Jun; Du, Hui; Zhong, Minxuan; Guo, Jiashi; Xie, Yao; Xiang, Yang; Wan, Jingyuan; Li, Ke] Chongqing Med Univ, Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing, Peoples R China; [Liu, Hao; Li, Nana; Kuang, Ge; Hu, Jun; Du, Hui; Guo, Jiashi; Xie, Yao; Xiang, Yang; Wan, Jingyuan] Chongqing Med Univ, Dept Pharmacol, Chongqing, Peoples R China; [Gong, Xia] Chongqing Med Univ, Dept Anat, Chongqing, Peoples R China; [Wang, Ting] Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 2, Chongqing, Peoples R China; [Wu, Shengwang] Army Med Univ, Xinqiao Hosp, Dept Hematol, Chongqing, Peoples R China; [Yuan, Yiling] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Clin Immunol Translat Med Key Lab Sichuan Prov, Chengdu, Peoples R China; [Yin, Xinru] Army Med Univ, Daping Hosp, Inst Surg Res, Dept Gastroenterol, Chongqing, Peoples R China; [Li, Ke] Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 1, Chongqing, Peoples R China"

通信作者："Wan, JY; Li, K (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing, Peoples R China."

来源：FREE RADICAL BIOLOGY AND MEDICINE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001125935800001

JCR分区：Q1

影响因子：7.4

年份：2024

卷号：210

期号：　

开始页：42

结束页：53

文献类型：Article; Early Access

关键词：Protectin D1; Non-alcoholic steatohepatitis; IRAK-M; Toll like receptor 4; n-3 polyunsaturated fatty acid

摘要："Non-alcoholic steatohepatitis (NASH) is a prevalent metabolic disease, characterized by the hepatic steatosis, inflammation, and fibrosis, which is lack of effective treatment currently. Protectin D1 (PTD1), a lipid mediator from omega-3 fatty acid docosahexaenoic acid (DHA), has displayed wide pharmacological actions including anti-inflammation in a variety of diseases, but the role of PTD1 on NASH remains unclear. In this study, using the methionine and choline deficient (MCD) fed NASH model, we explored the effect and underlying mechanism of PTD1 on NASH in mice. Our results showed PTD1 improved MCD-induced steatosis, hepatocellular injury, inflammation and fibrosis. Furthermore, PTD1 inhibited MCD-induced activation of TLR4 downstream molecules (TAK1, p38 and p65) without affecting the levels of TLR4 and phosphorylated IRAK-1. Notably, the levels of IRAK-M protein and the binding between IRAK-M and TRAF6 in the liver were also increased by PTD1 in NASH mice. Moreover, IRAK-M knockout remarkedly reverted the beneficial effects of PTD1 on the NASH in mice. Thus, these results demonstrated that PTD1 could protect mice from NASH by inhibiting the activation of TLR4 downstream signaling pathway, which might be related to the upregulation of IRAK-M, indicating that PTD1 may provide a new treatment for NASH."

基金机构："Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202300403]; National Natural Science Foundation of China [81902293, 81600455]; China Postdoctoral Science Foundation [2022CQBSHTB3016]; Postdoc Research Funding; [2022M702604]"

基金资助正文："This study research was funded by the Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJQN202300403) , the National Natural Science Foundation of China (No.81902293 and 81600455) , Postdoc Research Funding (No. 2022CQBSHTB3016) , China Postdoctoral Science Foundation (No. <EM><STRONG> </STRONG></EM>2022M702604). The author sincerely acknowledges and thank our colleagues for their contributions."