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, regulating numerous ion channels and transporters, and promoting cell survival under stress. SGK1 tightly regulates multiple signal transduction pathways, which are related to various biological processes and diseases [1,4].

Genetic deficiency of Sgk1 in mice significantly reduced phosphate-induced calcification and osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs), and aortic calcification, stiffness, and osteo-/chondrogenic transdifferentiation in mice following cholecalciferol overload were strongly reduced by genetic knockout or pharmacological inhibition of Sgk1. Also, Sgk1 deficiency blunted vascular calcification in apolipoprotein E-deficient mice after subtotal nephrectomy, indicating SGK1 as a key regulator of vascular calcification, at least partly, via NF-κB activation [2]. In the context of liver ischemia-reperfusion in colorectal liver metastasis mouse models, administration of the SGK1 inhibitor GSK-650394 reduced ERK-related neutrophil extracellular traps formation and polymorphonuclear myeloid-derived suppressor cell infiltration, alleviating recurrence of liver metastasis [3]. In mice with high-fat diet-induced lung fibrosis, treatment with the SGK1 specific inhibitor EMD638683 alleviated pulmonary fibrosis and activation of the integrin-inflammasome pathway [5].

In conclusion, SGK1 plays essential roles in multiple biological processes. Through gene knockout or inhibitor-based studies in mouse models, its key regulatory functions in vascular calcification, recurrence of liver metastasis, and lung fibrosis have been revealed. These findings provide important insights into the mechanisms of related diseases and potential therapeutic targets.