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Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy

The human fibroblast growth factor (FGF) family comprises 22 structurally related polypeptides that play crucial roles in neuronal functions, development, and metabolism. FGFs are classified as intracrine, paracrine, and endocrine FGFs based on their action mechanisms. Paracrine and endocrine FGFs a...

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Autores principales: Itoh, Nobuyuki, Ohta, Hiroya, Konishi, Morichika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586497/
https://www.ncbi.nlm.nih.gov/pubmed/26483756
http://dx.doi.org/10.3389/fendo.2015.00154
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author Itoh, Nobuyuki
Ohta, Hiroya
Konishi, Morichika
author_facet Itoh, Nobuyuki
Ohta, Hiroya
Konishi, Morichika
author_sort Itoh, Nobuyuki
collection PubMed
description The human fibroblast growth factor (FGF) family comprises 22 structurally related polypeptides that play crucial roles in neuronal functions, development, and metabolism. FGFs are classified as intracrine, paracrine, and endocrine FGFs based on their action mechanisms. Paracrine and endocrine FGFs are secreted signaling molecules by acting via cell-surface FGF receptors (FGFRs). Paracrine FGFs require heparan sulfate as a cofactor for FGFRs. In contrast, endocrine FGFs, comprising FGF19, FGF21, and FGF23, require α-Klotho or β-Klotho as a cofactor for FGFRs. Endocrine FGFs, which are specific to vertebrates, lost heparan sulfate-binding affinity and acquired a systemic signaling system with α-Klotho or β-Klotho during early vertebrate evolution. The phenotypes of endocrine FGF knockout mice indicate that they play roles in metabolism including bile acid, energy, and phosphate/active vitamin D metabolism. Accumulated evidence for the involvement of endocrine FGFs in human genetic and metabolic diseases also indicates their pathophysiological roles in metabolic diseases, potential risk factors for metabolic diseases, and useful biomarkers for metabolic diseases. The therapeutic utility of endocrine FGFs is currently being developed. These findings provide new insights into the physiological and pathophysiological roles of endocrine FGFs and potential diagnostic and therapeutic strategies for metabolic diseases.
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spelling pubmed-45864972015-10-19 Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy Itoh, Nobuyuki Ohta, Hiroya Konishi, Morichika Front Endocrinol (Lausanne) Endocrinology The human fibroblast growth factor (FGF) family comprises 22 structurally related polypeptides that play crucial roles in neuronal functions, development, and metabolism. FGFs are classified as intracrine, paracrine, and endocrine FGFs based on their action mechanisms. Paracrine and endocrine FGFs are secreted signaling molecules by acting via cell-surface FGF receptors (FGFRs). Paracrine FGFs require heparan sulfate as a cofactor for FGFRs. In contrast, endocrine FGFs, comprising FGF19, FGF21, and FGF23, require α-Klotho or β-Klotho as a cofactor for FGFRs. Endocrine FGFs, which are specific to vertebrates, lost heparan sulfate-binding affinity and acquired a systemic signaling system with α-Klotho or β-Klotho during early vertebrate evolution. The phenotypes of endocrine FGF knockout mice indicate that they play roles in metabolism including bile acid, energy, and phosphate/active vitamin D metabolism. Accumulated evidence for the involvement of endocrine FGFs in human genetic and metabolic diseases also indicates their pathophysiological roles in metabolic diseases, potential risk factors for metabolic diseases, and useful biomarkers for metabolic diseases. The therapeutic utility of endocrine FGFs is currently being developed. These findings provide new insights into the physiological and pathophysiological roles of endocrine FGFs and potential diagnostic and therapeutic strategies for metabolic diseases. Frontiers Media S.A. 2015-09-29 /pmc/articles/PMC4586497/ /pubmed/26483756 http://dx.doi.org/10.3389/fendo.2015.00154 Text en Copyright © 2015 Itoh, Ohta and Konishi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Itoh, Nobuyuki
Ohta, Hiroya
Konishi, Morichika
Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy
title Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy
title_full Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy
title_fullStr Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy
title_full_unstemmed Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy
title_short Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy
title_sort endocrine fgfs: evolution, physiology, pathophysiology, and pharmacotherapy
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586497/
https://www.ncbi.nlm.nih.gov/pubmed/26483756
http://dx.doi.org/10.3389/fendo.2015.00154
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