FoxO1, short for Forkhead box O1, is a key transcription factor. It is involved in diverse cellular processes, regulating genes related to cell cycle, apoptosis, DNA repair, and oxidative stress. It plays a crucial role in the insulin→PI3K→Akt signaling pathway [2]. FoxO1 is important in maintaining the homeostasis of various tissues and is associated with numerous diseases, such as fibrosis, cancer, and metabolic disorders [2,3,4,5,6]. Genetic models, like KO/CKO mouse models, are valuable for studying FoxO1's functions.

In endometrial remodeling and homeostasis, FoxO1 is a cell-specific core transcription factor. In endometrial stromal cells, it is a decidualization marker, regulating the transcription of relevant genes. Epithelial FoxO1 is a novel endometrial receptivity marker. Loss of FoxO1 function in endometrial epithelial cells can cause neoplasia [1]. In hepatocyte-specific FoxO1 deletion (F1KO) mice, FoxO1 deficiency protects from liver fibrosis by reducing inflammation and TGF-β1-mediated HSC activation, indicating its role in liver fibrosis [2]. In group 3 innate lymphoid cells (ILC3s), FOXO1 deficiency drives hyperactivation of ILC3s and gut inflammation, showing its role in intestinal homeostasis [7].

In conclusion, FoxO1 is essential for maintaining tissue homeostasis in various organs. Through model-based research, especially KO/CKO mouse models, we've learned that FoxO1 plays significant roles in endometrial biology, liver fibrosis, and intestinal homeostasis. Understanding FoxO1's functions provides potential therapeutic targets for related diseases, such as endometrial neoplasia, liver fibrosis, and gut inflammation [1,2,7].

References:

1. Adiguzel, Dileyra, Celik-Ozenci, Ciler. . FoxO1 is a cell-specific core transcription factor for endometrial remodeling and homeostasis during menstrual cycle and early pregnancy. In Human reproduction update, 27, 570-583. doi:10.1093/humupd/dmaa060. https://pubmed.ncbi.nlm.nih.gov/33434267/

2. Pan, Quan, Gao, Mingming, Kim, DaMi, Qi, Yajuan, Guo, Shaodong. 2023. Hepatocyte FoxO1 Deficiency Protects From Liver Fibrosis via Reducing Inflammation and TGF-β1-mediated HSC Activation. In Cellular and molecular gastroenterology and hepatology, 17, 41-58. doi:10.1016/j.jcmgh.2023.08.013. https://pubmed.ncbi.nlm.nih.gov/37678798/

3. Xin, Zhenlong, Ma, Zhiqiang, Hu, Wei, Jia, Guozhan, Yang, Yang. 2017. FOXO1/3: Potential suppressors of fibrosis. In Ageing research reviews, 41, 42-52. doi:10.1016/j.arr.2017.11.002. https://pubmed.ncbi.nlm.nih.gov/29138094/

4. Shi, Feiyu, Li, Tian, Liu, Zhi, Xia, Hongping, She, Junjun. 2017. FOXO1: Another avenue for treating digestive malignancy? In Seminars in cancer biology, 50, 124-131. doi:10.1016/j.semcancer.2017.09.009. https://pubmed.ncbi.nlm.nih.gov/28965871/

5. Ebrahimnezhad, Mohammad, Natami, Mohammad, Bakhtiari, Ghazaleh Hafezi, Yousefi, Bahman, Majidinia, Maryam. 2023. FOXO1, a tiny protein with intricate interactions: Promising therapeutic candidate in lung cancer. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 169, 115900. doi:10.1016/j.biopha.2023.115900. https://pubmed.ncbi.nlm.nih.gov/37981461/

6. Benchoula, Khaled, Arya, Aditya, Parhar, Ishwar S, Hwa, Wong Eng. 2020. FoxO1 signaling as a therapeutic target for type 2 diabetes and obesity. In European journal of pharmacology, 891, 173758. doi:10.1016/j.ejphar.2020.173758. https://pubmed.ncbi.nlm.nih.gov/33249079/

7. Shao, Fei, Liu, Zhen, Wei, Qinglin, Fan, Zusen, Wang, Shuo. 2023. FOXO1 orchestrates the intestinal homeostasis via neuronal signaling in group 3 innate lymphoid cells. In The Journal of experimental medicine, 220, . doi:10.1084/jem.20230133. https://pubmed.ncbi.nlm.nih.gov/37549024/