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MiR-30c/PGC-1β protects against diabetic cardiomyopathy via PPARα
BACKGROUND: Metabolic abnormalities have been implicated as a causal event in diabetic cardiomyopathy (DCM). However, the mechanisms underlying cardiac metabolic disorder in DCM were not fully understood. RESULTS: Db/db mice, palmitate treated H9c2 cells and primary neonatal rat cardiomyocytes were...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329097/ https://www.ncbi.nlm.nih.gov/pubmed/30635067 http://dx.doi.org/10.1186/s12933-019-0811-7 |
Sumario: | BACKGROUND: Metabolic abnormalities have been implicated as a causal event in diabetic cardiomyopathy (DCM). However, the mechanisms underlying cardiac metabolic disorder in DCM were not fully understood. RESULTS: Db/db mice, palmitate treated H9c2 cells and primary neonatal rat cardiomyocytes were employed in the current study. Microarray data analysis revealed that PGC-1β may play an important role in DCM. Downregulation of PGC-1β relieved palmitate induced cardiac metabolism shift to fatty acids use and relevant lipotoxicity in vitro. Bioinformatics coupled with biochemical validation was used to confirm that PGC-1β was one of the direct targets of miR-30c. Remarkably, overexpression of miR-30c by rAAV system improved glucose utilization, reduced excessive reactive oxygen species production and myocardial lipid accumulation, and subsequently attenuated cardiomyocyte apoptosis and cardiac dysfunction in db/db mice. Similar effects were also observed in cultured cells. More importantly, miR-30c overexpression as well as PGC-1β knockdown reduced the transcriptional activity of PPARα, and the effects of miR-30c on PPARα was almost abated by PGC-1β knockdown. CONCLUSIONS: Our data demonstrated a protective role of miR-30c in cardiac metabolism in diabetes via targeting PGC-1β, and suggested that modulation of PGC-1β by miR-30c may provide a therapeutic approach for DCM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12933-019-0811-7) contains supplementary material, which is available to authorized users. |
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