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HEPARITIN SULFATE --- LIVER --- PROSTATE --- FIBROBLAST GROWTH FACTOR

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Fibroblast growth factors. --- Receptors, Fibroblast Growth Factor. --- Fibroblast Growth Factor 2. --- Cartilage-Derived Growth Factor --- Class II Heparin-Binding Growth Factor --- FGF-2 --- FGF2 --- Fibroblast Growth Factor-2 --- Heparin-Binding Growth Factor Class II --- Prostate Epithelial Cell Growth Factor --- Prostatropin --- Basic Fibroblast Growth Factor --- Fibroblast Growth Factor, Basic --- HBGF-2 --- Cartilage Derived Growth Factor --- FGF 2 --- FGF Receptor --- Fibroblast Growth Factor Receptor --- Heparin-Binding Growth Factor Receptor --- FGF Receptors --- Fibroblast Growth Factor Receptors --- Receptors, FGF --- Heparin Binding Growth Factor Receptor --- Receptor, FGF --- Fibroblast Growth Factors --- Fibroblast growth factor --- Growth factors --- Mitogens

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FGF19 (fibroblastes growth factor) and its murine homologue FGF15 are members of the subfamily of FGF19 with endocrine action. FGF15 and 19 have a similar expression pattern and they regulate glucose metabolism and bile acids (BA) in a similar way. FGF15/19 plays a cruciale role in the regulating the bile acid pool. Indeed, its expression is induced in the intestine by the acid receptor FXR (Farnesoid X Receptor). FGF15/19 is then released into the circulation and inhibits the expression of CYp7al (the rate-limiting enzyme in the classical pathway of BA synthesis) in the liver. Iker Uriarte et al. Pinpointed that FGF15 is a critical hormone in modulating the rate of BA during liver regeneration. Therefore, we questioned whether FGF15/19 could have an impact on the proliferation and differentiation of progenitor cells into hepatocytes and cholangiocytes. In order to assess this hypothesis we evaluated the effect of recombinant FGF19 (r FGF19) injections on progenitor cells in a murine model hepatotocixity. We exposed C57BL/6J mice to a choline-deficient, ethionine-supplemented diet (CDE) during 23 days to stimulate expansion of progenitor cells.During the last 11 days mice were injected with PBS or rFGF19.This preliminary experiment showed that: 1) rFGF19 injections are well tolerated, 2) the rFGF19 is active in mice, it is detected in treated mice’s serum (whereas it’s undetectable in control mice) and inhibits effectively the expression of Cyp7al in the liver. By using the localization in the CDE model we did not observe any evident effect produced by rFGF19: LPC seem to have a similar localization in the CDE mice treated with rFGF19 compared to thecontrols. Moreover, both mice groups present a comparable number of LPC. We could continue our study by analyzing the effects in a different mouse model (OPN-iCreERT2; Rosa26RYFP- that allows tracking the fate of progenitor cells, so as to evaluate the impact of FGF19 on the differentiation of progenitor cells in hepatocytes. Le FGF19 (facteur de croissance des fibroblastes – fibroblastes growth factor) ou son homologue murin, FGF15 sont membres de la sous famille du FGF19 à action endocrine. Les ARN messagers (ARNm) de FGF15 et FGF19 sont des profils d’expression similaires et régulent de la même façon le métabolisme du glucose et des acides biliaires. FGF15/ FGF19 joue un rôle important dans la régulation du pool des acides biliaires. En effet, son expression est induite dans l’intestin par le récepteur aux acides biliaires FXR (Farnesoid X Receptor). Il est alors relargué dans la circulation et va inhiber l’expression de CYp7al dans le foie, enzyme de synthèse des acides biliaires. Iker Uriarte et al. ont identifié FGF15 comme une hormone essentielle dans la modulation du taux de BA au cours de la régénération du foie. Nous proposons que le FGF15 pourrait influencer la prolifération et la différenciation des cellules progénitrices en hépatocytes et cholangiocytes. Pour évaluer cette question nous avons évalué l’effet de l’administration de FGF19 recombinant sur les cellules progénitrices dans un modèle murin d’hépatotoxicité. Nous avons exposé des souris C57BL6J à un régime déficient en choline supplémentée en éthionine (CDE), pendant 23 jours pour induire l’expansion des cellules progénitrices. Pendant les 11 derniers jours, les souris ont été injectées avec du rFGF19 humain ou du PBS. Cette expérience préliminaire a permis de montrer que 1) les injections de rFGF19 sont bien tolérées, 2) que le rFGF19 est fonctionnel chez la souris : il est détecté dans le sérum des souris traitées (indétectables dans les souris contrôles) et inhibe bien l’expression de Cyp7al dans le foie. Dans un modèle d’induction des cellules progénitrices, nous n’avons pas observé d’effet évident du rFGF19 : les LPC semblent aussi nombreuses et ont une localisation similaire chez les souris CDE traitées au rFGF19 ou non. On pourrait continuer notre étude en allant à analyser la réponse de modèle des souris différents (OPN-IcreERT2 ; Rosa26RYFP) qui permet de suivre le devenir des cellules progénitrices, et ainsi d’évaluer l’effet de FGF19 sur la différenciation des cellules pro génitrices en hépatocytes.

fibroblast growth factor 15, mouse --- FGF19 protein, human --- Hematopoietic Stem Cells --- Liver Regeneration --- Review

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

FGF (fibroblast growth factor) --- regeneration --- development --- metabolic regulation --- ischema-reperfusion injury

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Crohn Disease --- Antibodies, Monoclonal --- Gastrointestinal Agents --- Intestinal Fistula --- Fibroblast Growth Factor 2 --- drug therapy. --- therapeutic use. --- complications. --- blood. --- Theses --- drug therapy --- therapeutic use --- complications --- blood