Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health.
Détails
Télécharger: 29203887_BIB_219FB1ADDEA8.pdf (5915.32 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_219FB1ADDEA8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health.
Périodique
Scientific reports
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
04/12/2017
Peer-reviewed
Oui
Volume
7
Numéro
1
Pages
16839
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12-21 week (adult) and 28-40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5´methyl-cytosine (5mC) level decrease. To further investigate miR-29 family role in the fish heart we generated a transgenic zebrafish model where miR-29 was knocked-down. In this model we found significant morphological and functional cardiac alterations and an impairment of oxygen dependent pathways by transcriptome analysis leading to hypoxic marker up-regulation. To get insights the possible hypoxic regulation of miR-29 family, we exposed human cardiac fibroblasts to 1% O <sub>2</sub> levels. In hypoxic condition we found miR-29 down-modulation responsible for the accumulation of collagens and 5mC. Overall, our data suggest that miR-29 family up-regulation might represent an endogenous mechanism aimed at ameliorating the age-dependent cardiac damage leading to hypertrophy and fibrosis.
Mots-clé
5-Methylcytosine/metabolism, Aging, Animals, Antagomirs/metabolism, Cell Hypoxia, Cell Line, Collagen/metabolism, DNA Methylation, Echocardiography, Fibroblasts/cytology, Fibroblasts/metabolism, Fishes/genetics, Heart/physiology, Humans, MicroRNAs/antagonists & inhibitors, MicroRNAs/genetics, MicroRNAs/metabolism, Myocardium/metabolism, Oxidative Stress, Up-Regulation, Zebrafish
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/12/2017 20:13
Dernière modification de la notice
30/04/2021 7:08