Igfbp2, Insulin-like growth factor binding protein 2, was first identified as an IGF system regulator, controlling the distribution, function, and activity of IGFs in the pericellular space [4]. It is a developmentally regulated gene, highly expressed in embryonic and fetal tissues and decreasing post-birth. Through binding and sequestering factors like IGF-II, it is involved in multiple biological processes and signaling pathways, playing a significant role in development and disease [3,4]. Genetic models such as gene knockout (KO) and conditional knockout (CKO) mouse models are valuable for studying its functions.

In lung fibrosis, intranasal delivery of recombinant IGFBP2 protects aged mice from weight loss and shows antifibrotic effects after bleomycin lung injury. Aged human-Igfbp2 transgenic mice have reduced senescence in alveolar epithelial type 2 (AEC2) cells and improved bleomycin-induced lung fibrosis. IGFBP2 expression is suppressed in AEC2 cells from fibrotic lung regions of patients with idiopathic pulmonary fibrosis (IPF) and/or pulmonary hypertension [1]. In the liver, Igfbp2-CreER knockin mice show that IGFBP2-expressing midlobular hepatocytes contribute to liver homeostasis and regeneration [2]. In breast cancer, adipocytes secrete IGFBP2, which inhibits breast cancer invasion by binding and sequestering cancer-derived IGF-II [3]. In glioma, knockdown of IGFBP2 in mice stops glioma progression and M2 macrophage polarization, indicating that the CAF-related gene IGFBP2 promotes glioma progression by inducing M2 macrophage polarization [5]. In diabetic kidney disease, deficiency of IGFBP2 in mice attenuates urine protein, renal pathological injury, and podocyte apoptosis [6].

In conclusion, Igfbp2 is involved in a variety of biological processes and disease conditions. Model-based research, especially KO/CKO mouse models, has revealed its role in lung fibrosis, liver homeostasis, breast cancer invasion, glioma progression, and diabetic kidney disease. Understanding Igfbp2's functions provides insights into disease mechanisms and potential therapeutic targets for these diseases [1,2,3,5,6].

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. Lin, Yu-Hsuan, Wei, Yonglong, Zeng, Qiyu, Wang, Tao, Zhu, Hao. . IGFBP2 expressing midlobular hepatocytes preferentially contribute to liver homeostasis and regeneration. In Cell stem cell, 30, 665-676.e4. doi:10.1016/j.stem.2023.04.007. https://pubmed.ncbi.nlm.nih.gov/37146585/

3. Conway, James R W, Dinç, Defne D, Follain, Gautier, Peuhu, Emilia, Ivaska, Johanna. 2023. IGFBP2 secretion by mammary adipocytes limits breast cancer invasion. In Science advances, 9, eadg1840. doi:10.1126/sciadv.adg1840. https://pubmed.ncbi.nlm.nih.gov/37436978/

4. 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/

5. 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/

6. Wang, Xiaochen, Zhang, Yifan, Chi, Kun, Zhu, Hanyu, Hong, Quan. 2024. IGFBP2 induces podocyte apoptosis promoted by mitochondrial damage via integrin α5/FAK in diabetic kidney disease. In Apoptosis : an international journal on programmed cell death, 29, 1109-1125. doi:10.1007/s10495-024-01974-1. https://pubmed.ncbi.nlm.nih.gov/38796567/