Igfbp2-KO Mouse

Igfbp2, or Insulin-like growth factor binding protein 2, was initially discovered as a regulator of the IGF system, controlling IGF distribution, function, and activity in the pericellular space. It is a developmentally regulated gene, highly expressed in embryonic and fetal tissues, and its expression markedly decreases after birth. IGFBP2 is involved in multiple signaling pathways, often acting independently of IGFs, and is considered an integrative hub of oncogenic signaling networks [2].

In the context of disease, loss-of-function studies have provided valuable insights. In lung fibrosis, intranasal delivery of recombinant IGFBP2 protected aged mice from weight loss and had antifibrotic effects after bleomycin lung injury. Aged human-Igfbp2 transgenic mice showed reduced senescence in alveolar epithelial type 2 cells and ameliorated bleomycin-induced lung fibrosis, suggesting that loss of IGFBP2 mediates alveolar type 2 cell senescence and promotes lung fibrosis [1]. In glioma, knockdown of the CAF-related gene IGFBP2 in mice halted glioma progression and M2 macrophage polarization, indicating that IGFBP2 promotes glioma progression through induction of M2 macrophage polarization [3]. In non-alcoholic fatty liver disease (NAFLD), IGFBP2 deficiency in knockout mice aggravated hepatic steatosis and NASH phenotypes, demonstrating that IGFBP2 functions as an endogenous protector against hepatic steatosis via suppression of the EGFR-STAT3 pathway [4].

In conclusion, Igfbp2 plays diverse and crucial roles in various biological processes and disease conditions. Gene knockout mouse models have been instrumental in uncovering its functions, such as in lung fibrosis, glioma, and NAFLD. These studies suggest that Igfbp2 could potentially be a therapeutic target for these diseases, highlighting the importance of further research on this gene.

References:

1. Chin, Chiahsuan, Ravichandran, Ranjithkumar, Sanborn, Kristina, Bremner, Ross M, Sureshbabu, Angara. 2023. Loss of IGFBP2 mediates alveolar type 2 cell senescence and promotes lung fibrosis. In Cell reports. Medicine, 4, 100945. doi:10.1016/j.xcrm.2023.100945. https://pubmed.ncbi.nlm.nih.gov/36787736/

2. Li, Tao, Forbes, M Elizabeth, Fuller, Gregory N, Yang, Xuejun, Zhang, Wei. 2020. IGFBP2: integrative hub of developmental and oncogenic signaling network. In Oncogene, 39, 2243-2257. doi:10.1038/s41388-020-1154-2. https://pubmed.ncbi.nlm.nih.gov/31925333/

3. Zhang, Xiaobin, Sun, Xiaolin, Guo, Chen, Li, Jianan, Liang, Guobiao. 2023. Cancer-associated fibroblast-associated gene IGFBP2 promotes glioma progression through induction of M2 macrophage polarization. In American journal of physiology. Cell physiology, 326, C252-C268. doi:10.1152/ajpcell.00234.2023. https://pubmed.ncbi.nlm.nih.gov/37982173/

4. Zhai, Tianyu, Cai, Liang, Jia, Xi, Li, Xiaoying, Xia, Pu. 2024. IGFBP2 functions as an endogenous protector against hepatic steatosis via suppression of the EGFR-STAT3 pathway. In Molecular metabolism, 89, 102026. doi:10.1016/j.molmet.2024.102026. https://pubmed.ncbi.nlm.nih.gov/39299533/