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Post-Transcriptional Control of Tropoelastin in Aortic Smooth Muscle Cells Affects Aortic Dissection Onset.
- Source :
- Molecules & Cells (Elsevier B.V); 2018, Vol. 41 Issue 3, p198-206, 9p
- Publication Year :
- 2018
-
Abstract
- Aortic dissection (AD) is a catastrophic disease with high mortality and morbidity, characterized with fragmentation of elastin and loss of smooth muscle cells. Although AD has been largely attributable to polymorphisms defect in the elastin-coding gene, tropoelastin (TE), other undermined factors also appear to play roles in AD onset. Here, we investigated the effects of post-transcriptional control of TE by microRNAs (miRNAs) on elastin levels in aortic smooth muscle cells (ASMC). We found that miR-144-3p is a miRNA that targets TE mRNA in both human and mouse. Bioinformatics analyses and dual luciferase reporter assay showed that miR-144-3p inhibited protein translation of TE, through binding to the 3'-UTR of the TE mRNA. Interestingly, higher miR-144-3p levels and lower TE were detected in the ASMC obtained from AD patients, compared to those from non-AD controls. In a mouse model for human AD, infusion of adeno-associated viruses (serotype 6) carrying antisense for miR-144-3p (asmiR-144-3p) under CAG promoter significantly reduced the incidence and severity of AD, seemingly through enhancement of TE levels in ASMC. Thus, our data suggest an essential role of miR-144-3p on the pathogenesis of AD. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10168478
- Volume :
- 41
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Molecules & Cells (Elsevier B.V)
- Publication Type :
- Academic Journal
- Accession number :
- 128894833
- Full Text :
- https://doi.org/10.14348/molcells.2018.2193