S100A2, a member of the EF-hand motif family S100, is a low-molecular-weight protein with two calcium-binding EF-hand-type domains. It is distributed in various organs such as mammary epithelial cells, glands, lungs, kidneys, and prostate gland, and is involved in multiple physiological and pathological processes [1]. S100A2 has been associated with cell proliferation, differentiation, and is linked to various pathways, though the exact pathways are still under investigation. Its study is crucial for understanding human disorders like inflammatory diseases and malignant tumors. Genetic models, especially KO/CKO mouse models, can provide insights into its functions.

In a study on renal interstitial fibrosis (RIF), elevated S100A2 levels were observed in three mouse models (unilateral ureteral obstruction, ischemia-reperfusion injury, and aristolochic acid nephropathy) and TGF-β1-treated HK-2 cells. siRNA silencing of S100A2 in cultured HK-2 cells suppressed the epithelial-mesenchymal transition (EMT) process and extracellular matrix (ECM) accumulation, while overexpression induced EMT and ECM deposition. S100A2-mediated EMT was found to depend on FoxO1 [2].

In conclusion, S100A2 plays significant roles in both normal biological processes related to cell proliferation and differentiation, and in disease conditions such as renal interstitial fibrosis. The use of mouse models, like those in the RIF study, has revealed its role in promoting fibrosis through the FoxO1-mediated EMT pathway, highlighting its potential as a therapeutic target in related diseases.