FoxO1, short for Forkhead box O1, is a crucial transcription factor mediating the insulin→PI3K→Akt signaling pathway. It governs diverse cellular processes such as cell cycle arrest, apoptosis, DNA repair, and oxidative stress, and is of great significance in maintaining cellular homeostasis [3,4]. Genetic models like KO/CKO mouse models are valuable tools for studying FoxO1's functions.

In endometrium, FoxO1 is a cell-specific core transcription factor. It serves as a decidualization marker in endometrial stromal cells, regulating the transcription of relevant genes. Epithelial FoxO1 is a novel endometrial receptivity marker. Loss-of-function of FOXO1 in endometrial epithelial cells can lead to neoplasia [1]. In hepatocytes, FoxO1 deficiency protects from liver fibrosis by reducing inflammation and TGF-β1-mediated HSC activation. Increased FoxO1 expression was observed in carbon tetrachloride-induced fibrosis [3]. In macrophages, down-regulated and deactivated FOXO1 signaling in aging macrophages is involved in age-related osteoporosis, and lipoteichoic acid can restrain macrophage senescence via the β-catenin/FOXO1/REDD1 pathway [2]. In group 3 innate lymphoid cells, FOXO1 deficiency drives hyperactivation of these cells, resulting in gut inflammation, and FOXO1 balances their activation via neuronal signaling to regulate intestinal homeostasis [5].

In summary, FoxO1 plays essential roles in multiple biological processes and disease conditions. Through model-based research, especially KO/CKO mouse models, we've learned that FoxO1 is crucial in endometrial remodeling, liver fibrosis prevention, macrophage senescence regulation, and intestinal homeostasis maintenance. These findings provide potential therapeutic targets for diseases like endometrial neoplasia, liver fibrosis, age-related osteoporosis, and gut inflammation [1,2,3,5].