Insulin-like growth factor-binding protein 5 (Igfbp5) is an important secretory protein. It is involved in multiple biological processes, and is related to the insulin-like growth factor receptor (IGF1R) pathway. It can form complexes with IGFs, regulating their bioavailability. Additionally, it has IGF-independent activities [3].

In disease models, Igfbp5 shows diverse effects. In diabetic kidney disease (DKD) mouse models, ablation of Igfbp5 alleviated kidney inflammation. Mechanistically, Igfbp5 enhanced endothelial glycolysis by activating EGR1 and increasing PFKFB3 expression, promoting DKD progression [1]. In glioblastoma, Igfbp5 knockdown in GSCs inhibited invasion, while overexpression enhanced it. Igfbp5 binds to ROR1, facilitating ROR1/HER2-CREB signaling for GSC invasion [2]. In myocardial ischemia mouse models, heart-specific Igfbp5 knockdown inhibited myocardial apoptosis and improved cardiac remodeling and function, regulating cardiomyocyte survival via the IGF1R/AKT pathway [4]. Deletion of endothelial Igfbp5 in hindlimb ischemic mice promoted angiogenesis, enhanced by ATP metabolism and HIF1α stabilization [5].

In summary, Igfbp5 plays crucial roles in various biological processes and disease conditions. Gene-knockout (KO) or conditional-knockout (CKO) mouse models have revealed its functions in diseases such as DKD, glioblastoma, myocardial ischemia, and angiogenesis-related disorders, providing potential therapeutic targets for these diseases.

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. 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/