Fibroblast growth factor 16: Molecular mechanisms, signalling crosstalk, and emerging roles in cardiac biology and metabolic regulation
Fibroblast growth factor (FGF) 16 is critically involved in embryonic heart development, adult cardiac homeostasis, and potentially in metabolic regulation. Initially recognized for its cardiac-specific role during embryogenesis, recent studies demonstrate that FGF16 significantly mitigates patholog...
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Elsevier
2025-08-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S104366182500283X |
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| author | Xiaodan Hui Qian Lin Kaiqing Liu Chunjie Gu Ahmed Abdelbaset-Ismail Kupper A. Wintergerst Zhongbin Deng Lu Cai Yi Tan |
| author_facet | Xiaodan Hui Qian Lin Kaiqing Liu Chunjie Gu Ahmed Abdelbaset-Ismail Kupper A. Wintergerst Zhongbin Deng Lu Cai Yi Tan |
| author_sort | Xiaodan Hui |
| collection | DOAJ |
| description | Fibroblast growth factor (FGF) 16 is critically involved in embryonic heart development, adult cardiac homeostasis, and potentially in metabolic regulation. Initially recognized for its cardiac-specific role during embryogenesis, recent studies demonstrate that FGF16 significantly mitigates pathological cardiac remodelling, such as fibrosis and hypertrophy, through competitive inhibition of FGF2-induced transforming growth factor-β1 signalling via FGF receptor 1c. Molecular investigations further indicate that FGF16 exerts cardioprotective effects primarily through activation of key intracellular pathways, including phosphoinositide 3-kinase/protein kinase B and protein kinase C, as well as regulation by transcription factors GATA binding protein 4, nuclear Factor kappa-light-chain-enhancer of activated B cells, and cardiac-specific homeobox/NK2 homeobox 5, and RNA methyltransferase-mediated N6-methyladenosine modifications. However, detailed mechanisms underlying receptor-specific interactions remain unclear. This review systematically summarizes the genomic organization, receptor selectivity, cardiac signalling mechanisms, and emerging metabolic roles of FGF16, critically evaluates the current evidence, identifies key research gaps, and highlights therapeutic potentials for cardiovascular and metabolic disorders. |
| format | Article |
| id | doaj-art-b5f7918c53c44505a1222a7ebc9e9b50 |
| institution | DOAJ |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-b5f7918c53c44505a1222a7ebc9e9b502025-08-20T03:13:42ZengElsevierPharmacological Research1096-11862025-08-0121810785810.1016/j.phrs.2025.107858Fibroblast growth factor 16: Molecular mechanisms, signalling crosstalk, and emerging roles in cardiac biology and metabolic regulationXiaodan Hui0Qian Lin1Kaiqing Liu2Chunjie Gu3Ahmed Abdelbaset-Ismail4Kupper A. Wintergerst5Zhongbin Deng6Lu Cai7Yi Tan8Pediatric Research Institute, Departments of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USATouchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USAPediatric Research Institute, Departments of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USAPediatric Research Institute, Departments of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USAPediatric Research Institute, Departments of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USAWendy Novak Diabetes Institute, Norton Children’s Hospital, Louisville, KY, USA; Norton Children’s Endocrinology, Department of Pediatrics, University of Louisville, Norton Children’s Hospital, Louisville, KY, USA; The Center for Integrative Environmental Health Sciences, University of Louisville School of Medicine, Louisville, KY, USADepartment of Surgery, Division of Immunotherapy, University of Louisville School of Medicine, KY, USA; Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USAPediatric Research Institute, Departments of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USA; Wendy Novak Diabetes Institute, Norton Children’s Hospital, Louisville, KY, USA; The Center for Integrative Environmental Health Sciences, University of Louisville School of Medicine, Louisville, KY, USA; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA; Department of Radiation Oncology, University of Louisville School of Medicine, Louisville, KY, USAPediatric Research Institute, Departments of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USA; Wendy Novak Diabetes Institute, Norton Children’s Hospital, Louisville, KY, USA; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA; Correspondence to: Pediatric Research Institute, 570 South Preston Street, Baxter I, Room 304E, Louisville, KY, USA.Fibroblast growth factor (FGF) 16 is critically involved in embryonic heart development, adult cardiac homeostasis, and potentially in metabolic regulation. Initially recognized for its cardiac-specific role during embryogenesis, recent studies demonstrate that FGF16 significantly mitigates pathological cardiac remodelling, such as fibrosis and hypertrophy, through competitive inhibition of FGF2-induced transforming growth factor-β1 signalling via FGF receptor 1c. Molecular investigations further indicate that FGF16 exerts cardioprotective effects primarily through activation of key intracellular pathways, including phosphoinositide 3-kinase/protein kinase B and protein kinase C, as well as regulation by transcription factors GATA binding protein 4, nuclear Factor kappa-light-chain-enhancer of activated B cells, and cardiac-specific homeobox/NK2 homeobox 5, and RNA methyltransferase-mediated N6-methyladenosine modifications. However, detailed mechanisms underlying receptor-specific interactions remain unclear. This review systematically summarizes the genomic organization, receptor selectivity, cardiac signalling mechanisms, and emerging metabolic roles of FGF16, critically evaluates the current evidence, identifies key research gaps, and highlights therapeutic potentials for cardiovascular and metabolic disorders.http://www.sciencedirect.com/science/article/pii/S104366182500283XFGF16Cardiac DevelopmentCardiac RemodellingMetabolic RegulationSignalling Crosstalk |
| spellingShingle | Xiaodan Hui Qian Lin Kaiqing Liu Chunjie Gu Ahmed Abdelbaset-Ismail Kupper A. Wintergerst Zhongbin Deng Lu Cai Yi Tan Fibroblast growth factor 16: Molecular mechanisms, signalling crosstalk, and emerging roles in cardiac biology and metabolic regulation Pharmacological Research FGF16 Cardiac Development Cardiac Remodelling Metabolic Regulation Signalling Crosstalk |
| title | Fibroblast growth factor 16: Molecular mechanisms, signalling crosstalk, and emerging roles in cardiac biology and metabolic regulation |
| title_full | Fibroblast growth factor 16: Molecular mechanisms, signalling crosstalk, and emerging roles in cardiac biology and metabolic regulation |
| title_fullStr | Fibroblast growth factor 16: Molecular mechanisms, signalling crosstalk, and emerging roles in cardiac biology and metabolic regulation |
| title_full_unstemmed | Fibroblast growth factor 16: Molecular mechanisms, signalling crosstalk, and emerging roles in cardiac biology and metabolic regulation |
| title_short | Fibroblast growth factor 16: Molecular mechanisms, signalling crosstalk, and emerging roles in cardiac biology and metabolic regulation |
| title_sort | fibroblast growth factor 16 molecular mechanisms signalling crosstalk and emerging roles in cardiac biology and metabolic regulation |
| topic | FGF16 Cardiac Development Cardiac Remodelling Metabolic Regulation Signalling Crosstalk |
| url | http://www.sciencedirect.com/science/article/pii/S104366182500283X |
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