FoxO1, short for Forkhead box O1, is a crucial transcription factor that mediates insulin→PI3K→Akt signaling, governing diverse cellular processes such as cell cycle arrest, apoptosis, and DNA repair [3,6]. It is involved in multiple biological functions like metabolism, cell differentiation, and maintaining tissue homeostasis, and is associated with various diseases including fibrosis, diabetes, obesity, and cancers [3,4,5,6,7]. Genetic models, especially KO/CKO mouse models, are valuable in studying its functions.

In endometrial research, FoxO1 is considered a decidualization marker in endometrial stromal cells as it regulates the transcription of decidual prolactin and insulin-like growth factor-binding protein 1 genes. Epithelial FoxO1 is a novel endometrial receptivity marker, and its loss of function causes endometrial neoplasia. In endothelium, its expression coincides with increased vascular permeabilization during early pregnancy [1].

In liver fibrosis studies, increased FoxO1 expression and activation were observed in carbon tetrachloride (CCL4)-induced fibrosis. Hepatic FoxO1 deletion in F1KO mice largely attenuated CCL4-induced liver injury, fibrosis, inflammation, and decreased TGF-β1 levels compared to control mice [3].

In age-related osteoporosis, FOXO1 signaling, which is downregulated in aging macrophages, plays a key role. Blocking FOXO1 signaling aggravates bone loss and macrophage senescence, while lipoteichoic acid treatment elevates FOXO1 signaling via the β-catenin pathway [2].

In the intestine, FOXO1 deficiency in ILC3s drives hyperactivation and gut inflammation. FOXO1 promotes the transcription of neuropeptide receptor VIPR2 and inhibits ADRA2A, balancing ILC3s activation [8].

In conclusion, FoxO1 is essential for maintaining physiological functions in multiple tissues. Model-based research, especially KO/CKO mouse models, has revealed its significant roles in endometrial remodeling, liver fibrosis, osteoporosis, and intestinal homeostasis. Understanding FoxO1 functions provides potential therapeutic targets for related diseases such as endometrial neoplasia, liver fibrosis, and age-related osteoporosis [1,2,3,8].