S100A2, a member of the S100 family of low-molecular-weight proteins, features two calcium-binding EF-hand-type domains. It is distributed across multiple organs like mammary epithelial cells, glands, lungs, kidneys, and prostate gland, interacting with diverse molecules and involved in various physiological and pathological actions, especially in inflammatory diseases and malignant tumors [1].

In the context of renal interstitial fibrosis (RIF), S100A2 was found to have elevated expression 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 accumulation, indicating that S100A2 activation exacerbates interstitial fibrosis in kidneys by facilitating FoxO1-mediated EMT [2].

In conclusion, S100A2 plays a significant role in both physiological and pathological conditions, especially in inflammatory and cancer-related processes. Mouse models, such as those used in the study of RIF, have been crucial in revealing its role in promoting interstitial fibrosis through the FoxO1-mediated EMT pathway, providing insights into potential therapeutic targets for related diseases.