DUSP9 alleviates hepatic ischemia/reperfusion injury by restraining both mitogen-activated protein kinase and IKK in an apoptosis signal-regulating kinase 1-dependent manner

作者全名："Li, Zhongtang; Huang, Zuotian; Luo, Yunhai; Yang, Hang; Yang, Mei"

作者地址："[Li, Zhongtang; Yang, Mei] Chongqing Med Univ, Coll Basic Med, Chongqing 400016, Peoples R China; [Luo, Yunhai; Yang, Hang] Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Huang, Zuotian] Chongqing Univ Canc Hosp, Dept Hepatobiliary, Pancreat Tumor Ctr, Chongqing 400030, Peoples R China"

通信作者："Yang, M (通讯作者)，Chongqing Med Univ, Coll Basic Med, Chongqing 400016, Peoples R China."

来源：ACTA BIOCHIMICA ET BIOPHYSICA SINICA

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000908873400005

JCR分区：Q2

影响因子：3.7

年份：2022

卷号：54

期号：12

开始页：1811

结束页：1821

文献类型：Article

关键词：DUSP9; hepatic ischemia/reperfusion injury; ASK1; IKK

摘要："Hepatic ischemia/reperfusion (I/R) injury occurs frequently in various liver operations and diseases, but its effective treatment remains inadequate because the key switch that leads to hepatic explosive inflammation has not been well disclosed. Dual specificity phosphatase 9 (DUSP9) is widely involved in the innate immune response of solid organs and is sometimes regulated by ubiquitin. In the present study, we find that DUSP9 is reduced in mouse hepatic I/R injury. DUSP9 enrichment attenuates hepatic inflammation both in vivo and in vitro as revealed by western blot analysis and qRT-PCR. In contrast, DUSP9 depletion leads to more severe I/R injury. Mechanistically, DUSP9 inhibits the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) by directly binding to ASK1, thereby decreasing tumor necrosis factor receptor-associated factor 6 (TRAF6), K63 ubiquitin and the phosphorylation of p38/JNK1 instead of ERK1. The present study documents a novel role of DUSP9 in hepatic I/R injury and implies the potential of targeting the DUSP9/ASK1 axis towards mitogen-activated protein kinase and TRAF6/inhibitor of kappa B kinase pathways."

基金机构：Natural Science Foundation of Chongqing (Postdoctoral Fund) [cstc2021jcyj-bsh0033]; Postdoctoral Research Foundation of Chongqing Medical University

基金资助正文：This work was supported by the grants from the Natural Science Foundation of Chongqing (Postdoctoral Fund) (No. cstc2021jcyj-bsh0033) and the Postdoctoral Research Foundation of Chongqing Medical University.