The role of fatty acid β-oxidation in lymphangiogenesis.

Détails

ID Serval
serval:BIB_4F842A3F3CD6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The role of fatty acid β-oxidation in lymphangiogenesis.
Périodique
Nature
Auteur(s)
Wong B.W., Wang X., Zecchin A., Thienpont B., Cornelissen I., Kalucka J., García-Caballero M., Missiaen R., Huang H., Brüning U., Blacher S., Vinckier S., Goveia J., Knobloch M., Zhao H., Dierkes C., Shi C., Hägerling R., Moral-Dardé V., Wyns S., Lippens M., Jessberger S., Fendt S.M., Luttun A., Noel A., Kiefer F., Ghesquière B., Moons L., Schoonjans L., Dewerchin M., Eelen G., Lambrechts D., Carmeliet P.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Statut éditorial
Publié
Date de publication
02/02/2017
Peer-reviewed
Oui
Volume
542
Numéro
7639
Pages
49-54
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Lymphatic vessels are lined by lymphatic endothelial cells (LECs), and are critical for health. However, the role of metabolism in lymphatic development has not yet been elucidated. Here we report that in transgenic mouse models, LEC-specific loss of CPT1A, a rate-controlling enzyme in fatty acid β-oxidation, impairs lymphatic development. LECs use fatty acid β-oxidation to proliferate and for epigenetic regulation of lymphatic marker expression during LEC differentiation. Mechanistically, the transcription factor PROX1 upregulates CPT1A expression, which increases acetyl coenzyme A production dependent on fatty acid β-oxidation. Acetyl coenzyme A is used by the histone acetyltransferase p300 to acetylate histones at lymphangiogenic genes. PROX1-p300 interaction facilitates preferential histone acetylation at PROX1-target genes. Through this metabolism-dependent mechanism, PROX1 mediates epigenetic changes that promote lymphangiogenesis. Notably, blockade of CPT1 enzymes inhibits injury-induced lymphangiogenesis, and replenishing acetyl coenzyme A by supplementing acetate rescues this process in vivo.
Mots-clé
Acetates/pharmacology, Acetyl Coenzyme A/metabolism, Acetylation/drug effects, Animals, Carnitine O-Palmitoyltransferase/antagonists & inhibitors, Carnitine O-Palmitoyltransferase/genetics, Carnitine O-Palmitoyltransferase/metabolism, Cell Differentiation/drug effects, Cell Differentiation/genetics, Endothelial Cells/cytology, Endothelial Cells/drug effects, Endothelial Cells/metabolism, Epigenesis, Genetic, Fatty Acids/chemistry, Fatty Acids/metabolism, Female, Histones/metabolism, Homeodomain Proteins/metabolism, Human Umbilical Vein Endothelial Cells, Humans, Lymphangiogenesis/drug effects, Lymphangiogenesis/genetics, Lymphatic Vessels/cytology, Lymphatic Vessels/drug effects, Lymphatic Vessels/metabolism, Mice, Mice, Inbred C57BL, Oxidation-Reduction/drug effects, Protein Biosynthesis, Transcription, Genetic, Tumor Suppressor Proteins/metabolism, Umbilical Arteries/cytology, Up-Regulation
Pubmed
Web of science
Création de la notice
25/05/2018 9:20
Dernière modification de la notice
20/08/2019 15:05
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