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...

Full description

Saved in:
Bibliographic Details
Main Authors: Xiaodan Hui, Qian Lin, Kaiqing Liu, Chunjie Gu, Ahmed Abdelbaset-Ismail, Kupper A. Wintergerst, Zhongbin Deng, Lu Cai, Yi Tan
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Pharmacological Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S104366182500283X
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849714426015383552
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
work_keys_str_mv AT xiaodanhui fibroblastgrowthfactor16molecularmechanismssignallingcrosstalkandemergingrolesincardiacbiologyandmetabolicregulation
AT qianlin fibroblastgrowthfactor16molecularmechanismssignallingcrosstalkandemergingrolesincardiacbiologyandmetabolicregulation
AT kaiqingliu fibroblastgrowthfactor16molecularmechanismssignallingcrosstalkandemergingrolesincardiacbiologyandmetabolicregulation
AT chunjiegu fibroblastgrowthfactor16molecularmechanismssignallingcrosstalkandemergingrolesincardiacbiologyandmetabolicregulation
AT ahmedabdelbasetismail fibroblastgrowthfactor16molecularmechanismssignallingcrosstalkandemergingrolesincardiacbiologyandmetabolicregulation
AT kupperawintergerst fibroblastgrowthfactor16molecularmechanismssignallingcrosstalkandemergingrolesincardiacbiologyandmetabolicregulation
AT zhongbindeng fibroblastgrowthfactor16molecularmechanismssignallingcrosstalkandemergingrolesincardiacbiologyandmetabolicregulation
AT lucai fibroblastgrowthfactor16molecularmechanismssignallingcrosstalkandemergingrolesincardiacbiologyandmetabolicregulation
AT yitan fibroblastgrowthfactor16molecularmechanismssignallingcrosstalkandemergingrolesincardiacbiologyandmetabolicregulation