期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-16829-w
关键词
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资金
- LOEWE Cell & Gene Therapy Center (LOEWE-CGT) Goethe University Frankfurt
- Deutsche Forschungsgemeinschaft Program [SFB834, B11]
- Start up grant from LOEWE-Forschungszentrum fur Zell- und Gentherapie, gefordert durch das Hessische Ministerium fur Wissenschaft und Kunst.Aktenzeichen [III L 5-518/17.004]
- August Scheidel-Stiftung
- Amandus und Barbara Pauli Stiftung
- LOEWE CGT grant - DFG (German Research Foundation) Excellence Cluster Cardio Pulmonary System [III L 5-518/17.004]
- project ETHERNA of the Fondazione Pisa
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-2 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.
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