Igfbp5, Insulin-like growth factor-binding protein 5, is an important secretory protein. It is involved in regulating the bioavailability of insulin-like growth factors (IGFs) by forming complexes with them. Additionally, it has IGF-independent activities. Igfbp5 is associated with multiple pathways such as the Hedgehog signaling pathway, PI3K-Akt signaling pathway, and is involved in biological processes like cell-matrix adhesion, extracellular matrix binding, and collagen binding [3,5].

In diabetic kidney disease (DKD), ablation of Igfbp5 alleviated kidney inflammation. Mechanistically, Igfbp5 increased endothelial glycolysis by activating EGR1 and enhancing PFKFB3 expression [1]. In glioblastoma, Igfbp5 binds to ROR1, promoting GSC invasion and tumorigenesis, and knockdown of Igfbp5 inhibited GSC invasion [2]. In myocardial ischemia, heart-specific Igfbp5 knockdown inhibited myocardial apoptosis and increased cardiomyocyte proliferation, and during chronic remodeling, it ameliorated pathological cardiac remodeling and dysfunction [4]. In ischaemic hindlimb injury, deletion of endothelial Igfbp5 promoted angiogenesis by enhancing ATP metabolism and stabilizing HIF1α [6].

In conclusion, Igfbp5 plays diverse roles in multiple biological processes and disease conditions. Gene-knockout (KO) and conditional-knockout (CKO) mouse models have been crucial in revealing its functions, such as in DKD, glioblastoma, myocardial ischemia, and ischaemic hindlimb injury. These studies provide insights into potential therapeutic targets for these diseases [1,2,4,6].

References:

1. Song, Chengcheng, Wang, Shuqiang, Fu, Zhangning, Wu, Di, Hong, Quan. 2022. IGFBP5 promotes diabetic kidney disease progression by enhancing PFKFB3-mediated endothelial glycolysis. In Cell death & disease, 13, 340. doi:10.1038/s41419-022-04803-y. https://pubmed.ncbi.nlm.nih.gov/35418167/

2. Lin, Weiwei, Niu, Rui, Park, Seong-Min, Park, Jong Bae, Yin, Jinlong. 2023. IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis. In Nature communications, 14, 1578. doi:10.1038/s41467-023-37306-1. https://pubmed.ncbi.nlm.nih.gov/36949068/

3. Dittmer, Jürgen. 2022. Biological effects and regulation of IGFBP5 in breast cancer. In Frontiers in endocrinology, 13, 983793. doi:10.3389/fendo.2022.983793. https://pubmed.ncbi.nlm.nih.gov/36093095/

4. Zhu, Qingqing, Lu, Xinyi, Chen, Mengli, Zhou, Yanli, Liao, Shengen. 2024. IGFBP5 affects cardiomyocyte survival and functional recovery in mice following myocardial ischemia. In Communications biology, 7, 1594. doi:10.1038/s42003-024-07304-0. https://pubmed.ncbi.nlm.nih.gov/39613849/

5. Deng, Yu, Yang, Xu, Hua, Hongzhong, Zhang, Cong. 2022. IGFBP5 is Upregulated and Associated with Poor Prognosis in Colorectal Cancer. In International journal of general medicine, 15, 6485-6497. doi:10.2147/IJGM.S370576. https://pubmed.ncbi.nlm.nih.gov/35966504/

6. Song, Fei, Hu, Yu, Hong, Yi-Xiang, Li, Gang, Wang, Yan. . Deletion of endothelial IGFBP5 protects against ischaemic hindlimb injury by promoting angiogenesis. In Clinical and translational medicine, 14, e1725. doi:10.1002/ctm2.1725. https://pubmed.ncbi.nlm.nih.gov/38886900/