SGK1, also known as serum and glucocorticoid-induced kinase-1, belongs to the AGC protein kinase family. It phosphorylates serine and threonine residues of target proteins, regulates numerous ion channels and transporters, and promotes cell survival under stress. SGK1 tightly controls multiple signal transduction pathways related to tumor development, vascular calcification, immune modulation, and fibrosis [1,2,4,5]. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.

In mouse models, genetic deficiency or pharmacological inhibition of SGK1 reduced phosphate-induced vascular calcification and osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs) [2]. In cholecalciferol-overloaded mice and apolipoprotein E-deficient mice after subtotal nephrectomy, genetic knockout or pharmacological inhibition of Sgk1 decreased aortic calcification, stiffness, and osteo-/chondrogenic transdifferentiation [2]. Hepatocyte SGK1 activated by hepatic ischemia-reperfusion promoted the recurrence of liver metastasis via IL-6/STAT3 in a mouse model, and the SGK1 inhibitor GSK-650394 alleviated this effect [3]. In mice with idiopathic pulmonary fibrosis, SGK1 aggravated the condition by triggering H3K27ac-mediated macrophage reprogramming and disturbing immune homeostasis [6].

In conclusion, SGK1 is a key regulator in multiple biological processes. Model-based research, especially using KO/CKO mouse models, has revealed its crucial roles in diseases such as vascular calcification, cancer recurrence, and pulmonary fibrosis. Understanding SGK1 functions provides potential therapeutic targets for these diseases.

References:

1. Ghani, Madiha Javeed. 2021. SGK1, autophagy and cancer: an overview. In Molecular biology reports, 49, 675-685. doi:10.1007/s11033-021-06836-6. https://pubmed.ncbi.nlm.nih.gov/34669124/

2. Voelkl, Jakob, Luong, Trang Td, Tuffaha, Rashad, Lang, Florian, Alesutan, Ioana. 2018. SGK1 induces vascular smooth muscle cell calcification through NF-κB signaling. In The Journal of clinical investigation, 128, 3024-3040. doi:10.1172/JCI96477. https://pubmed.ncbi.nlm.nih.gov/29889103/

3. Li, Xiangdong, Wang, Ziyi, Jiao, Chenyu, Han, Sheng, Pu, Liyong. 2023. Hepatocyte SGK1 activated by hepatic ischemia-reperfusion promotes the recurrence of liver metastasis via IL-6/STAT3. In Journal of translational medicine, 21, 121. doi:10.1186/s12967-023-03977-z. https://pubmed.ncbi.nlm.nih.gov/36788538/

4. Sang, Yiwen, Kong, Piaoping, Zhang, Shizhen, Tao, Zhihua, Liu, Weiwei. 2021. SGK1 in Human Cancer: Emerging Roles and Mechanisms. In Frontiers in oncology, 10, 608722. doi:10.3389/fonc.2020.608722. https://pubmed.ncbi.nlm.nih.gov/33542904/

5. Lu, Run-Qing, Zhang, Yin-Yin, Zhao, Hai-Qiu, Jiang, Zhong-Xing, Guo, Rong. 2022. SGK1, a Critical Regulator of Immune Modulation and Fibrosis and a Potential Therapeutic Target in Chronic Graft-Versus-Host Disease. In Frontiers in immunology, 13, 822303. doi:10.3389/fimmu.2022.822303. https://pubmed.ncbi.nlm.nih.gov/35222400/

6. Wu, Jianzhi, Gong, Liping, Li, Yijie, Gu, Xiaohong, Li, Xiaojiaoyang. 2024. SGK1 aggravates idiopathic pulmonary fibrosis by triggering H3k27ac-mediated macrophage reprogramming and disturbing immune homeostasis. In International journal of biological sciences, 20, 968-986. doi:10.7150/ijbs.90808. https://pubmed.ncbi.nlm.nih.gov/38250161/