Fbln7-KO Mouse

Fbln7, an adhesion protein secreted into the extracellular matrix, functions in multiple biological processes. Structurally similar to short fibulins but lacking elastogenic abilities, it has been associated with various pathways including those related to cell adhesion, growth, motility, and survival. Genetic models, such as knockout mice, have been crucial in understanding its functions [3,4,5].

In cardiac remodeling, Fbln7 deletion attenuated post-myocardial infarction (MI) cardiac remodeling, leading to better cardiac function and reduced myocardial fibrosis. It binds to the epidermal growth factor receptor (EGFR) and activates downstream focal adhesion kinase/AKT signaling, causing fibroblast-to-myofibroblast transdifferentiation [1]. In hypertension-related vascular remodeling, Fbln7 knockout mice showed attenuated angiotensin II-induced vascular remodeling, while smooth muscle-specific overexpression exacerbated it. Fbln7 promotes vascular smooth muscle cell (VSMC) phenotypic transformation from contractile to synthetic by interacting with syndecan-4 (SDC4) [2]. In acute kidney injury, Fbln7KO mice were protected from calcium oxalate (CaOx)-induced kidney damage, suggesting Fbln7 mediates local CaOx deposition and renal tubular epithelium damage [3].

In conclusion, Fbln7 plays significant roles in cardiac remodeling, vascular remodeling, and acute kidney injury. Gene knockout mouse models have been instrumental in revealing these functions, highlighting Fbln7 as a potential therapeutic target in these disease areas.

References:

1. Zheng, Xuehui, Liu, Lingxin, Liu, Jing, Yao, Guoqing, Bu, Peili. 2023. Fibulin7 Mediated Pathological Cardiac Remodeling through EGFR Binding and EGFR-Dependent FAK/AKT Signaling Activation. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2207631. doi:10.1002/advs.202207631. https://pubmed.ncbi.nlm.nih.gov/37344348/

2. Yao, Guoqing, Zheng, Xuehui, Hu, Yang, Ti, Yun, Bu, Pei Li. 2024. FBLN7 mediates vascular smooth muscle cell phenotype switching and vascular remodeling in hypertension. In Theranostics, 14, 7569-7588. doi:10.7150/thno.102593. https://pubmed.ncbi.nlm.nih.gov/39659565/

3. Sugiura, Hidekazu, Tsunezumi, Jun, Yanagisawa, Hiromi, Nitta, Kosaku, Tsuchiya, Ken. 2022. Fibulin7 aggravates calcium oxalate-induced acute kidney injury by binding to calcium oxalate crystals. In Journal of cellular physiology, 238, 165-178. doi:10.1002/jcp.30914. https://pubmed.ncbi.nlm.nih.gov/36370444/

4. Tsunezumi, Jun, Sugiura, Hidekazu, Oinam, Lalhaba, Kuro-O, Makoto, Yanagisawa, Hiromi. 2018. Fibulin-7, a heparin binding matricellular protein, promotes renal tubular calcification in mice. In Matrix biology : journal of the International Society for Matrix Biology, 74, 5-20. doi:10.1016/j.matbio.2018.04.014. https://pubmed.ncbi.nlm.nih.gov/29730503/

5. Chakraborty, Papiya, Dash, Shiba Prasad, Sarangi, Pranita P. 2020. The role of adhesion protein Fibulin7 in development and diseases. In Molecular medicine (Cambridge, Mass.), 26, 47. doi:10.1186/s10020-020-00169-z. https://pubmed.ncbi.nlm.nih.gov/32429873/