Igfbp7, or Insulin-like growth factor-binding protein 7, is involved in multiple biological processes. It can interact with insulin-like growth factors, modulating their activities, and is associated with pathways such as the FGF2/FGFR1/PI3K/AKT, Akt-mTOR, and JAK/STAT pathways. It plays a role in various biological functions including cell proliferation, invasion, and senescence, and is relevant to numerous diseases [1,3,5,6]. Genetic models, like gene knockout (KO) models, are valuable for studying Igfbp7.

In a zebrafish NAFLD model, depletion of Igfbp7 significantly alleviated liver steatosis, inflammation, and fibrosis, suggesting that Igfbp7 promotes NAFLD progression through regulating ferroptosis [4]. In murine studies, EC-specific deletion of Igfbp7 ameliorated cardiac dysfunction, indicating that Igfbp7 produced by senescent endothelial cells causes cardiac dysfunction [2]. In gastric cancer, IGFBP7 deficiency inhibited cell proliferation and migration in vitro, and in a nude mouse model, down-regulation of IGFBP7 suppressed tumorigenesis [5].

In conclusion, Igfbp7 is crucial in processes like cell growth regulation, senescence, and in diseases such as non-alcoholic fatty liver disease, heart failure, and gastric cancer. Studies using KO or conditional knockout (CKO) mouse models have revealed its specific roles in these disease conditions, providing insights into potential therapeutic targets for treatment.

References:

1. Li, Dandan, Xia, Lingyun, Huang, Pan, Leng, Weidong, Qin, Shanshan. 2023. Cancer-associated fibroblast-secreted IGFBP7 promotes gastric cancer by enhancing tumor associated macrophage infiltration via FGF2/FGFR1/PI3K/AKT axis. In Cell death discovery, 9, 17. doi:10.1038/s41420-023-01336-x. https://pubmed.ncbi.nlm.nih.gov/36681667/

2. Katoh, Manami, Nomura, Seitaro, Yamada, Shintaro, Aburatani, Hiroyuki, Komuro, Issei. 2024. Vaccine Therapy for Heart Failure Targeting the Inflammatory Cytokine Igfbp7. In Circulation, 150, 374-389. doi:10.1161/CIRCULATIONAHA.123.064719. https://pubmed.ncbi.nlm.nih.gov/38991046/

3. Chen, Zhe, Li, Lei, Wu, Weiru, Hou, Yu, Song, Guanbin. 2020. Exercise protects proliferative muscle satellite cells against exhaustion via the Igfbp7-Akt-mTOR axis. In Theranostics, 10, 6448-6466. doi:10.7150/thno.43577. https://pubmed.ncbi.nlm.nih.gov/32483463/

4. Wang, Yanqin, Bo, Jiaqi, Zhao, Zhonghua, Zhang, Qianqian, Liu, Lixin. 2023. Depletion of Igfbp7 alleviates zebrafish NAFLD progression through inhibiting hepatic ferroptosis. In Life sciences, 332, 122086. doi:10.1016/j.lfs.2023.122086. https://pubmed.ncbi.nlm.nih.gov/37714372/

5. Mo, Weilie, Deng, Lijian, Cheng, Yun, Ge, Sen, Wang, Jin. . IGFBP7 regulates cell proliferation and migration through JAK/STAT pathway in gastric cancer and is regulated by DNA and RNA methylation. In Journal of cellular and molecular medicine, 28, e70080. doi:10.1111/jcmm.70080. https://pubmed.ncbi.nlm.nih.gov/39351597/

6. Siraj, Yesuf, Aprile, Domenico, Alessio, Nicola, Di Bernardo, Giovanni, Galderisi, Umberto. 2024. IGFBP7 is a key component of the senescence-associated secretory phenotype (SASP) that induces senescence in healthy cells by modulating the insulin, IGF, and activin A pathways. In Cell communication and signaling : CCS, 22, 540. doi:10.1186/s12964-024-01921-2. https://pubmed.ncbi.nlm.nih.gov/39533382/