Mst1, also known as mammalian sterile 20-like kinase 1, belongs to the serine/threonine protein kinase superfamily and is a key component of the mechanosensitive Hippo pathway. It plays vital roles in inflammation, immunity, and various physiological and pathological processes. In inflammation, it generally aggravates inflammatory injury via pathways like MST1-JNK, MST1-mROS, MST1-Foxo3, and NF-κB, along with regulatory factors such as TNF-α, MIEF1, and LPS [1]. In immunity, it balances immune activation and tolerance through regulating multiple pathways and molecules [1].

In an atherosclerosis model, mice with EC-specific Mst1 deficiency (Mst1iECKOApoE-/-) showed that inhibition of the MST1-Cx43 axis drives oscillatory shear stress-induced endothelial dysfunction and atherosclerosis, suggesting MST1 as a potential therapeutic target [2]. In non-alcoholic fatty liver disease (NAFLD), genetic ablation of Mst1 in mice attenuated HFD-mediated hepatic injury, indicating Mst1's role in disrupting Parkin-related mitophagy in NAFLD [3].

In conclusion, Mst1 is a crucial regulator in multiple biological processes. Studies using gene knockout (KO) or conditional knockout (CKO) mouse models have revealed its significance in diseases such as atherosclerosis and NAFLD, providing potential therapeutic directions for these conditions.

References:

1. Li, Tongfen, Wen, Yiqiong, Lu, Qiongfen, Zheng, Yuanyuan, Sun, Shibo. 2023. MST1/2 in inflammation and immunity. In Cell adhesion & migration, 17, 1-15. doi:10.1080/19336918.2023.2276616. https://pubmed.ncbi.nlm.nih.gov/37909712/

2. Quan, Meixi, Lv, Huizhen, Liu, Zening, Zhu, Yi, Ai, Ding. 2022. MST1 Suppresses Disturbed Flow Induced Atherosclerosis. In Circulation research, 131, 748-764. doi:10.1161/CIRCRESAHA.122.321322. https://pubmed.ncbi.nlm.nih.gov/36164986/

3. Zhou, Tao, Chang, Ling, Luo, Yi, Zhou, Ying, Zhang, Jianjun. 2019. Mst1 inhibition attenuates non-alcoholic fatty liver disease via reversing Parkin-related mitophagy. In Redox biology, 21, 101120. doi:10.1016/j.redox.2019.101120. https://pubmed.ncbi.nlm.nih.gov/30708325/