Fgf2-KO Mouse

Fgf2, also known as fibroblast growth factor 2 or basic fibroblast growth factor (bFGF), is a key growth factor involved in multiple biological processes. It binds to FGF receptors (FGFR) to initiate various signaling pathways, playing a crucial role in cell growth, differentiation, angiogenesis, and tissue repair. Genetic models, such as gene knockout mice, have been instrumental in studying its functions [2,3,4,5,6,7].

In a study on acute kidney injury (AKI), inducible, renal tubule-specific atg7 knockout (iRT-atg7-KO) mice showed that autophagy deficiency after AKI suppressed the pro-fibrotic phenotype in tubular cells and reduced fibrosis by specifically diminishing FGF2. This indicates that persistent autophagy after AKI induces FGF2 expression and secretion in tubular cells, leading to fibroblast activation and renal fibrosis [1]. In bone homeostasis, FGF2-deficient bone marrow stromal cells (BMSCs) exhibited higher mineralization capability and lower osteoclastogenic gene expression. Correspondingly, FGF2-knockout mice showed increased bone mass and attenuated expression of osteoclast-related markers, suggesting that FGF2 positively regulates osteoclastogenesis via the ERK-CREB pathway [3]. Fgf2 knockout mice also showed decreased alcohol consumption and failed to show alcohol-conditioned place preference, indicating that endogenous FGF2 is a positive regulator of alcohol-drinking behaviors [4].

In conclusion, Fgf2 is essential for a variety of biological functions including tissue repair, bone homeostasis, and regulation of alcohol-related behaviors. The use of Fgf2 KO mouse models has significantly contributed to understanding its role in renal fibrosis, bone-related disorders, and alcohol-use disorder, providing potential targets for treating these conditions.

References:

1. Livingston, Man J, Shu, Shaoqun, Fan, Ying, Venkatachalam, Manjeri A, Dong, Zheng. 2022. Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis. In Autophagy, 19, 256-277. doi:10.1080/15548627.2022.2072054. https://pubmed.ncbi.nlm.nih.gov/35491858/

2. Pallotta, Maria Teresa, Nickel, Walter. 2020. FGF2 and IL-1β - explorers of unconventional secretory pathways at a glance. In Journal of cell science, 133, . doi:10.1242/jcs.250449. https://pubmed.ncbi.nlm.nih.gov/33154173/

3. Wen, Xin, Hu, Geng, Xiao, Xue, Liu, Qingxin, Li, Haifang. 2022. FGF2 positively regulates osteoclastogenesis via activating the ERK-CREB pathway. In Archives of biochemistry and biophysics, 727, 109348. doi:10.1016/j.abb.2022.109348. https://pubmed.ncbi.nlm.nih.gov/35835230/

4. Even-Chen, Oren, Herburg, Leonie, Kefalakes, Ekaterini, Grothe, Claudia, Barak, Segev. 2021. FGF2 is an endogenous regulator of alcohol reward and consumption. In Addiction biology, 27, e13115. doi:10.1111/adb.13115. https://pubmed.ncbi.nlm.nih.gov/34796591/

5. Du, Chao, Davis, John S, Chen, Chao, Yang, Li-Guo, Hua, Guo-Hua. . FGF2/FGFR signaling promotes cumulus-oocyte complex maturation in vitro. In Reproduction (Cambridge, England), 161, 205-214. doi:10.1530/REP-20-0264. https://pubmed.ncbi.nlm.nih.gov/33434172/

6. Wang, Rongli, Wang, Lijun, Wang, Lihui, Wang, Wei, Yang, Xinyuan. 2022. FGF2 Is Protective Towards Cisplatin-Induced KGN Cell Toxicity by Promoting FTO Expression and Autophagy. In Frontiers in endocrinology, 13, 890623. doi:10.3389/fendo.2022.890623. https://pubmed.ncbi.nlm.nih.gov/35784556/

7. Boye, Carly, Christensen, Kyle, Asadipour, Kamal, Francis, Michael, Bulysheva, Anna. 2021. Gene electrotransfer of FGF2 enhances collagen scaffold biocompatibility. In Bioelectrochemistry (Amsterdam, Netherlands), 144, 107980. doi:10.1016/j.bioelechem.2021.107980. https://pubmed.ncbi.nlm.nih.gov/34847373/