FGF/FGFR signaling in health and disease

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Abstract

Growing evidences suggest that the fibroblast growth factor/FGF receptor (FGF/FGFR) signaling has crucial roles in a multitude of processes during embryonic development and adult homeostasis by regulating cellular lineage commitment, differentiation, proliferation, and apoptosis of various types of cells. In this review, we provide a comprehensive overview of the current understanding of FGF signaling and its roles in organ development, injury repair, and the pathophysiology of spectrum of diseases, which is a consequence of FGF signaling dysregulation, including cancers and chronic kidney disease (CKD). In this context, the agonists and antagonists for FGF-FGFRs might have therapeutic benefits in multiple systems.

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Origin and physiological roles of inflammation.

Ruslan Medzhitov (2008)

Inflammation underlies a wide variety of physiological and pathological processes. Although the pathological aspects of many types of inflammation are well appreciated, their physiological functions are mostly unknown. The classic instigators of inflammation - infection and tissue injury - are at one end of a large range of adverse conditions that induce inflammation, and they trigger the recruitment of leukocytes and plasma proteins to the affected tissue site. Tissue stress or malfunction similarly induces an adaptive response, which is referred to here as para-inflammation. This response relies mainly on tissue-resident macrophages and is intermediate between the basal homeostatic state and a classic inflammatory response. Para-inflammation is probably responsible for the chronic inflammatory conditions that are associated with modern human diseases.

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A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer.

David Hunter, Peter Kraft, Kevin B. Jacobs … (2007)

We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (P(trend) for the most strongly associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci.

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Fibroblast Growth Factor 21 Reverses Hepatic Steatosis, Increases Energy Expenditure, and Improves Insulin Sensitivity in Diet-Induced Obese Mice

Jing-Jing Xu, David J. B. Lloyd, Clarence Hale … (2009)

OBJECTIVE—Fibroblast growth factor 21 (FGF21) has emerged as an important metabolic regulator of glucose and lipid metabolism. The aims of the current study are to evaluate the role of FGF21 in energy metabolism and to provide mechanistic insights into its glucose and lipid-lowering effects in a high-fat diet–induced obesity (DIO) model. RESEARCH DESIGN AND METHODS—DIO or normal lean mice were treated with vehicle or recombinant murine FGF21. Metabolic parameters including body weight, glucose, and lipid levels were monitored, and hepatic gene expression was analyzed. Energy metabolism and insulin sensitivity were assessed using indirect calorimetry and hyperinsulinemic-euglycemic clamp techniques. RESULTS—FGF21 dose dependently reduced body weight and whole-body fat mass in DIO mice due to marked increases in total energy expenditure and physical activity levels. FGF21 also reduced blood glucose, insulin, and lipid levels and reversed hepatic steatosis. The profound reduction of hepatic triglyceride levels was associated with FGF21 inhibition of nuclear sterol regulatory element binding protein-1 and the expression of a wide array of genes involved in fatty acid and triglyceride synthesis. FGF21 also dramatically improved hepatic and peripheral insulin sensitivity in both lean and DIO mice independently of reduction in body weight and adiposity. CONCLUSIONS—FGF21 corrects multiple metabolic disorders in DIO mice and has the potential to become a powerful therapeutic to treat hepatic steatosis, obesity, and type 2 diabetes.

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Author and article information

Contributors

Yangli Xie: xieyangli841015@163.com

Huabing Qi: hbqi3@163.com

Lin Chen:

ORCID: http://orcid.org/0000-0001-7764-9412

linchen70@163.com

Journal

Journal ID (nlm-ta): Signal Transduct Target Ther

Journal ID (iso-abbrev): Signal Transduct Target Ther

Title: Signal Transduction and Targeted Therapy

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 2095-9907

ISSN (Electronic): 2059-3635

Publication date (Electronic): 2 September 2020

Publication date PMC-release: 2 September 2020

Publication date Collection: 2020

Volume: 5

Electronic Location Identifier: 181

Affiliations

[1 ]GRID grid.414048.d, ISNI 0000 0004 1799 2720, Desartment of Wound Repair and Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, , Army Medical University, ; Chongqing, China

[2 ]GRID grid.264763.2, ISNI 0000 0001 2112 019X, Department of Biomedical Sciences, , Texas A&M University College of Dentistry, ; Dallas, TX 75246 USA

Author information

Shuo Huang http://orcid.org/0000-0001-9495-4339

Lin Chen http://orcid.org/0000-0001-7764-9412

Article

Publisher ID: 222

DOI: 10.1038/s41392-020-00222-7

PMC ID: 7468161

PubMed ID: 32879300

SO-VID: 0da18e12-3773-4306-bf62-ce87cd761cf9

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 1 April 2020

Date revision received : 28 May 2020

Date accepted : 15 June 2020

Funding

Funded by: The National Key Research and Development Program of China (2018YFA0800802), National Natural Science Foundation of China (81530071, 81772306, 81721001, 81991513), Innovative Research Team in University (IRT1216) and Key research and development projects of science and technology innovation of social undertakings and people’s livelihood security in Chongqing (cstc2017shms-zdyfX0027).

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Keywords: diseases,developmental biology

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Keywords: diseases, developmental biology

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FGF/FGFR signaling in health and disease

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Most cited references 661

Origin and physiological roles of inflammation.

A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer.

Fibroblast Growth Factor 21 Reverses Hepatic Steatosis, Increases Energy Expenditure, and Improves Insulin Sensitivity in Diet-Induced Obese Mice

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