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In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
09:53

In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge

Published on: June 15, 2018

MicroRNAs involved in the mitogen-activated protein kinase cascades pathway during glucose-induced cardiomyocyte

E Shen1, Xuehong Diao, Xiaoxia Wang

  • 1Department of Ultrasound in Medicine, Shanghai Jiaotong University Affiliated 6th People's Hospital, Shanghai, China.

The American Journal of Pathology
|June 28, 2011
PubMed

Insights

Diabetic cardiomyopathy involves cardiac hypertrophy, a condition influenced by microRNAs (miRNAs). This study identified novel miRNAs and pathways, like MAPK signaling, involved in diabetic heart changes and hypertrophy.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Endocrinology

Background:

  • Diabetic cardiomyopathy, a late-stage diabetes complication, features cardiac hypertrophy.
  • MicroRNAs (miRNAs) are implicated in diabetic cardiac hypertrophy, necessitating further investigation into novel miRNAs.
  • Understanding these molecular mechanisms is crucial for therapeutic development.

Purpose of the Study:

  • To identify novel microRNAs (miRNAs) involved in diabetic cardiomyopathy and cardiac hypertrophy.
  • To elucidate the role of specific signaling pathways, particularly MAPK, in hyperglycemia-induced cardiomyocyte changes.
  • To investigate the regulatory relationship between miR-373, its target MEF2C, and the p38 pathway in diabetic conditions.

Main Methods:

  • Diabetic cardiomyopathy was induced in mice using streptozotocin.
  • Microarray analysis of myocardial tissue identified differentially expressed miRNAs.
  • Real-time PCR validated miRNA expression; bioinformatics predicted mRNA targets and enriched pathways (GO, KEGG).
  • In vitro studies exposed neonatal rat cardiomyocytes to high glucose and transfected them with miR-373 mimic.

Main Results:

  • Microarray analysis identified 19 differentially expressed miRNAs, with 16 validated by real-time PCR.
  • Bioinformatics analysis revealed enrichment in 31 Gene Ontology (GO) functions and 16 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, notably the MAPK signaling pathway.
  • In vivo and in vitro studies confirmed upregulation of ERK1/2, JNK, and p38 in cardiomyocyte hypertrophy during hyperglycemia.
  • Overexpression of miR-373 in cardiomyocytes reduced cell size and MEF2C levels, with miR-373 expression regulated by p38.

Conclusions:

  • MicroRNAs play a significant role in the pathogenesis of diabetic cardiomyopathy.
  • The MAPK signaling pathway, particularly p38, is a key regulator of hyperglycemia-induced cardiomyocyte hypertrophy.
  • miR-373 acts as a protective factor by reducing cell size and targeting MEF2C, with its expression modulated by p38.
  • Bioinformatics analysis is a reliable tool for uncovering mechanisms underlying diabetic cardiomyopathy.

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