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. Besides, it has IGF-independent activities. Igfbp5 is associated with multiple biological processes such as inflammation, fibrosis, and cell survival, and is involved in pathways like the insulin-like growth factor 1 (IGF1) receptor pathway, Hedgehog signaling pathway, and PI3K-Akt signaling pathway [1,3,5,7].

In disease-related studies, gene-knockout models have provided insights. Ablation of Igfbp5 alleviated kidney inflammation in diabetic kidney disease (DKD) mice. Igfbp5 enhanced kidney inflammation through metabolic reprogramming of glomerular endothelial cells by activating EGR1 and enhancing PFKFB3 expression [1]. In glioblastoma, knockdown of Igfbp5 inhibited GSC invasion [2]. Heart-specific Igfbp5 knockdown in mice with myocardial infarction inhibited myocardial apoptosis and increased cardiomyocyte proliferation, and during the chronic remodeling stage, it ameliorated pathological cardiac remodeling and dysfunction [4]. Deletion of endothelial Igfbp5 in mice promoted angiogenesis, protecting against ischaemic hindlimb injury [6].

In conclusion, Igfbp5 plays diverse roles in biological processes. The use of Igfbp5 KO/CKO mouse models has revealed its significance in diseases including DKD, glioblastoma, myocardial infarction, and ischaemic hindlimb injury. These findings contribute to understanding disease mechanisms and suggest potential therapeutic targets related to Igfbp5 [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/

7. Guo, Shenglong, Lei, Qi, Yang, Qian, Chen, Ruili. 2024. IGFBP5 Promotes Neuronal Apoptosis in a 6-OHDA-Toxicant Model of Parkinson's Disease by Inhibiting the Sonic Hedgehog Signaling Pathway. In Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 33, 269-280. doi:10.1159/000538467. https://pubmed.ncbi.nlm.nih.gov/38565090/