Fgf2, also known as fibroblast growth factor 2 or basic fibroblast growth factor (bFGF), is a significant protein involved in multiple biological processes. It binds with FGF receptors (FGFR) to initiate various functions. Fgf2 lacks an N-terminal secretory signal peptide and is secreted via an unconventional pathway [2]. It plays crucial roles in growth, development, and tissue repair, and is involved in pathways such as the ERK-CREB pathway [3].

In gene knockout studies, Fgf2-deficient bone marrow stromal cells (BMSCs) had higher mineralization capability and lower osteoclastogenic gene expression, and Fgf2-knockout mice showed increased bone mass, suggesting Fgf2 positively regulates osteoclastogenesis via the ERK-CREB pathway [3]. In addition, Fgf2 knockout mice had decreased alcohol consumption, failed to show alcohol-conditioned place preference, and had altered ethanol metabolism, indicating that endogenous Fgf2 is a positive regulator of alcohol-drinking behaviors [4]. In inducible, renal tubule-specific atg7 knockout (iRT-atg7-KO) mice, autophagy deficiency after acute kidney injury (AKI) suppressed FGF2 production in tubular cells, reducing fibrosis, suggesting that persistent autophagy after AKI induces FGF2 expression and secretion, which activates fibroblasts for renal fibrosis [1].

In conclusion, Fgf2 is essential in processes like bone homeostasis, alcohol-related behaviors, and renal fibrosis post-AKI. The use of Fgf2 knockout or conditional knockout mouse models has been instrumental in revealing its role in these specific disease-related areas, providing valuable insights into potential therapeutic targets for conditions such as osteoporosis, alcohol use disorder, and renal fibrosis.