DUSP12 protects against hepatic ischemia–reperfusion injury dependent on ASK1-JNK/p38 pathway in vitro and in vivo. Issue 17 (3rd September 2020)

• Record Type: Journal Article
• Authors: Qiu, Tao; Wang, Tianyu; Zhou, Jiangqiao; Chen, Zhongbao; Zou, Jilin; Zhang, Long; Ma, Xiaoxiong
• Is Part Of: Clinical science. Volume 134:Issue 17(2020)
• Page Start: 2279
• Page End: 2294
• Publication Date: 2020-09-03
• Subjects: ASK1 -- DUSP12 -- ischemia/reperfusion injury -- liver -- ubiquitination; Medicine -- Periodicals; Biochemistry -- Periodicals; 616
• DOI: 10.1042/CS20191272
• Languages: English
• ISSNs: 0143-5221

Abstract

Abstract: Hepatic ischemia–reperfusion (I/R) injury is an important risk factor resulting in liver failure during liver surgery. However, there is still lack of effective therapeutic methods to treat hepatic I/R injury. DUSP12 is a member of the dual specific phosphatase (DUSP) family. Some DUSPs have been identified as being involved in the regulation of hepatic I/R injury. However, the role of DUSP12 during hepatic I/R injury is still unclear. In the present study, we observed a significant decrease in DUSP12 expression in a hepatic I/R injury mouse model in vivo and in hypoxia/reoxygenation (H/R) model in vitro . Using hepatocyte-specific DUSP12 knockout mice and DUSP12 transgenic mice, we demonstrated that DUSP12 apparently relieved I/R-induced liver injury. Moreover, DUSP12 inhibited hepatic inflammatory responses and alleviated apoptosis both in vitro and in vivo . Furthermore, we demonstrated that JNK and p38 activity, but not ERK1/2, was increased in the DUSP12-deficient mice and decreased in the DUSP12 transgenic mice under I/R condition. ASK1 was required for DUSP12 function in hepatic I/R injury and inhibition of ASK1 prevented inflammation and apoptosis in DUSP12-deficient hepatocytes and mice. In conclusion, DUSP12 protects against hepatic I/R injury and related inflammation and apoptosis. This regulatory role of DUSP12 is primarily through ASK1-JNK/p38 signaling pathway. Taken together, DUSP12 could be a potential therapeutic target for hepatic I/R injury.