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Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice
- Source :
- Cell Research
- Publication Year :
- 2011
- Publisher :
- Springer Science and Business Media LLC, 2011.
-
Abstract
- Recent studies have begun to reveal critical roles of microRNAs (miRNAs) in the pathogenesis of cardiac hypertrophy and dysfunction. In this study, we tested whether a transforming growth factor-β (TGF-β)-regulated miRNA played a pivotal role in the development of cardiac hypertrophy and heart failure (HF). We observed that miR-27b was upregulated in hearts of cardiomyocyte-specific Smad4 knockout mice, which developed cardiac hypertrophy. In vitro experiments showed that the miR-27b expression could be inhibited by TGF-β1 and that its overexpression promoted hypertrophic cell growth, while the miR-27b suppression led to inhibition of the hypertrophic cell growth caused by phenylephrine (PE) treatment. Furthermore, the analysis of transgenic mice with cardiomyocyte-specific overexpression of miR-27b revealed that miR-27b overexpression was sufficient to induce cardiac hypertrophy and dysfunction. We validated the peroxisome proliferator-activated receptor-γ (PPAR-γ) as a direct target of miR-27b in cardiomyocyte. Consistently, the miR-27b transgenic mice displayed significantly lower levels of PPAR-γ than the control mice. Furthermore, in vivo silencing of miR-27b using a specific antagomir in a pressure-overload-induced mouse model of HF increased cardiac PPAR-γ expression, attenuated cardiac hypertrophy and dysfunction. The results of our study demonstrate that TGF-β1-regulated miR-27b is involved in the regulation of cardiac hypertrophy, and validate miR-27b as an efficient therapeutic target for cardiac diseases.
- Subjects :
- Genetically modified mouse
PPAR-γ
medicine.medical_specialty
Peroxisome proliferator-activated receptor
Cardiomegaly
Mice, Transgenic
Mice
Downregulation and upregulation
Transforming Growth Factor beta
Internal medicine
medicine
Animals
Gene silencing
Myocytes, Cardiac
Molecular Biology
Smad4 Protein
chemistry.chemical_classification
microRNA
biology
cardiac hypertrophy
therapeutic target
Cell Biology
Transforming growth factor beta
medicine.disease
transgenic mouse
MicroRNAs
Endocrinology
chemistry
Heart failure
Knockout mouse
biology.protein
Original Article
Transforming growth factor
Subjects
Details
- ISSN :
- 17487838 and 10010602
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Cell Research
- Accession number :
- edsair.doi.dedup.....cfe5b07c2455a08a173e5021d1c65c6b