Serum-and glucocorticoid-induced kinase 3 (SGK3), ubiquitously expressed in mammals, is regulated by estrogens and androgens. It is activated by insulin and growth factors via signaling pathways involving phosphatidylinositol-3-kinase (PI3K), 3-phosphoinositide-dependent kinase-1 (PDK-1), and mammalian target of rapamycin complex 2 (mTORC2). Activated SGK3 regulates numerous ion channels, carriers, receptors, and Na+/K+-ATPase, contributing to the transportation of various substances and multiple physiological and pathophysiological processes [1].

In a uremic mouse model, SGK3 was found to be upregulated in the certified outflow veins of arteriovenous fistulas (AVF) and aortas, and its activation promoted vascular calcification in chronic kidney disease (CKD) by enhancing the expression and activities of Pit-1 [2]. In macrophage-related studies, SGK3-deficient macrophages in a cardiac remodeling model established by angiotensin II (Ang II) infusion in mice attenuated Ang II-induced macrophage infiltration, myocardial hypertrophy, fibrosis, and mitochondrial oxidative stress, suggesting SGK3's role in hypertensive cardiac remodeling [3]. In the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) mouse models, SGK3 regulated TOPK phosphorylation to mediate the profibrotic phenotype of renal tubular epithelial cells (TECs), macrophage plasticity, and the crosstalk between TECs and macrophages [4].

In conclusion, SGK3 is a key regulator in multiple biological processes related to substance transportation and physiological balance. Model-based research, especially the use of KO/CKO mouse models, has revealed its significant roles in diseases such as CKD, hypertensive cardiac remodeling, and the AKI-CKD transition, providing potential therapeutic targets for these conditions.