Fgf12, belonging to the fibroblast growth factor homologous factors (FHF) subfamily (also known as the FGF11 subfamily), is an intracrine factor. Structurally, its core domain has high homology to other FGF proteins, adopting a β-trefoil structure. It is expressed in various tissues, especially excitable cells like neurons and cardiomyocytes. Fgf12 has multiple functions including interacting with sodium channels, signaling proteins, regulating the cytoskeletal system, binding to FGF receptors to prevent apoptosis, and being involved in ribosome biogenesis [2,4].

In mouse models, myeloid-specific Fgf12 knockout showed that deletion of Fgf12 in macrophages protected against bile duct ligation (BDL)-induced and CCL4-induced liver fibrosis. Fgf12 deletion decreased the population of certain macrophages in fibrotic liver tissue and reduced pro-inflammatory cytokines and chemokines. Fgf12 promoted pro-inflammatory activation of macrophages and HSC activation mainly through the monocyte chemoattractant protein-1/chemokine (C-C motif) receptor 2 axis, mediated by the Janus kinase-signal transducer of activators of transcription pathway [1]. In the imiquimod (IMQ)-induced psoriasis model, specific loss of Fgf12 in keratinocytes alleviated psoriasis-like symptoms and reduced proliferation. In vitro, knockdown of Fgf12 arrested the cell cycle and inhibited cell proliferation by regulating the p53 signaling pathway [3].

In summary, Fgf12 plays diverse roles in biological processes. Gene knockout mouse models have revealed its functions in liver fibrosis and psoriasis, suggesting its potential as a therapeutic target for these diseases. Additionally, it is associated with nervous system disorders, cancers, and cardiac diseases, further emphasizing its importance in disease-related research [2,5,6].

References:

1. Li, Santie, Zhou, Bin, Xue, Mei, Jin, Litai, Cong, Weitao. 2023. Macrophage-specific FGF12 promotes liver fibrosis progression in mice. In Hepatology (Baltimore, Md.), 77, 816-833. doi:10.1002/hep.32640. https://pubmed.ncbi.nlm.nih.gov/35753047/

2. Biadun, Martyna, Karelus, Radoslaw, Krowarsch, Daniel, Opalinski, Lukasz, Zakrzewska, Malgorzata. 2023. FGF12: biology and function. In Differentiation; research in biological diversity, 139, 100740. doi:10.1016/j.diff.2023.100740. https://pubmed.ncbi.nlm.nih.gov/38042708/

3. Wang, Nan, Xu, Xiejun, Guan, Fangqian, Cong, Weitao, Zhu, Zhongxin. 2024. FGF12 Positively Regulates Keratinocyte Proliferation by Stabilizing MDM2 and Inhibiting p53 Activity in Psoriasis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2400107. doi:10.1002/advs.202400107. https://pubmed.ncbi.nlm.nih.gov/39234815/

4. Sochacka, Martyna, Karelus, Radoslaw, Opalinski, Lukasz, Otlewski, Jacek, Zakrzewska, Malgorzata. 2022. FGF12 is a novel component of the nucleolar NOLC1/TCOF1 ribosome biogenesis complex. In Cell communication and signaling : CCS, 20, 182. doi:10.1186/s12964-022-01000-4. https://pubmed.ncbi.nlm.nih.gov/36411431/

5. Abraham, Anna, Ramsey, Keri, Belnap, Newell, Huentelman, Matthew, Narayanan, Vinodh. 2024. FGF12 copy number variant associated with epileptic encephalopathy. In Clinical genetics, 106, 114-115. doi:10.1111/cge.14542. https://pubmed.ncbi.nlm.nih.gov/38715525/

6. Ohori, Sachiko, Miyauchi, Akihiko, Osaka, Hitoshi, Fujita, Atsushi, Matsumoto, Naomichi. 2023. Biallelic structural variations within FGF12 detected by long-read sequencing in epilepsy. In Life science alliance, 6, . doi:10.26508/lsa.202302025. https://pubmed.ncbi.nlm.nih.gov/37286232/