Dusp14, also known as MKP6, is a MAP kinase phosphatase that plays crucial roles in regulating various cellular processes. It is involved in multiple pathways, such as the MAPKs and NF-κB pathways, and is of great biological importance in maintaining metabolic homeostasis, suppressing inflammation, and protecting against oxidative stress and cell death [1-5, 7, 9, 10]. Genetically modified mouse models have been valuable tools for studying its functions.

In multiple disease models, Dusp14 shows protective effects. In hepatocyte-specific Dusp14 knockout (HKO) and transgenic (TG) mice, Dusp14 was found to reduce cell death, ameliorate inflammation, and promote hepatocyte proliferation in hepatic ischaemia-reperfusion injury, by suppressing NF-κB and MAPK signalling via interacting with Tak1 [1]. In high-fat diet-induced or genetically obese mouse models, hepatocyte-specific Dusp14 overexpression (DUSP14-HTG) significantly ameliorated insulin resistance, hepatic lipid accumulation, and inflammatory responses, while DUSP14-HKO aggravated these pathological alterations by regulating the Tak1-JNK/p38/NF-κB axis [2]. In Dusp14-KO mice, cardiac IR injury was accelerated, with increased infarction area, apoptosis, and cardiac dysfunction, due to the activation of NF-κB and MAPKs signalling pathways modulated by ROS generation [3].

In conclusion, Dusp14 is essential for maintaining metabolic homeostasis, suppressing inflammation, and protecting against oxidative stress-related injuries in various tissues. Gene knockout mouse models have revealed its role in diseases such as hepatic ischaemia-reperfusion injury, non-alcoholic fatty liver disease, and cardiac IR injury, providing potential therapeutic targets for these conditions.

References:

1. Wang, Xiaozhan, Mao, Wenzhe, Fang, Chun, Huang, Zan, Li, Hongliang. 2017. Dusp14 protects against hepatic ischaemia-reperfusion injury via Tak1 suppression. In Journal of hepatology, , . doi:10.1016/j.jhep.2017.08.032. https://pubmed.ncbi.nlm.nih.gov/28887166/

2. Wang, Siyuan, Yan, Zhen-Zhen, Yang, Xia, She, Zhi-Gang, Tang, Yi-Da. 2018. Hepatocyte DUSP14 maintains metabolic homeostasis and suppresses inflammation in the liver. In Hepatology (Baltimore, Md.), 67, 1320-1338. doi:10.1002/hep.29616. https://pubmed.ncbi.nlm.nih.gov/29077210/

3. Lin, Bin, Xu, Jing, Feng, De-Guang, Wang, Jia-Xiang, Zhao, Hui. 2018. DUSP14 knockout accelerates cardiac ischemia reperfusion (IR) injury through activating NF-κB and MAPKs signaling pathways modulated by ROS generation. In Biochemical and biophysical research communications, 501, 24-32. doi:10.1016/j.bbrc.2018.04.101. https://pubmed.ncbi.nlm.nih.gov/29660332/