Cardiac transcriptome profiling of diabetic Akita mice using microarray and next generation sequencing

Varun Kesherwani, Hamid R. Shahshahan, Paras Kumar Mishra

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Although diabetes mellitus (DM) causes cardiomyopathy and exacerbates heart failure, the underlying molecular mechanisms for diabetic cardiomyopathy/heart failure are poorly understood. Insulin2 mutant (Ins2+/-) Akita is a mouse model of T1DM, which manifests cardiac dysfunction. However, molecular changes at cardiac transcriptome level that lead to cardiomyopathy remain unclear. To understand the molecular changes in the heart of diabetic Akita mice, we profiled cardiac transcriptome of Ins2+/- Akita and Ins2+/+ control mice using next generation sequencing (NGS) and microarray, and determined the implications of differentially expressed genes on various heart failure signaling pathways using Ingenuity pathway (IPA) analysis. First, we validated hyperglycemia, increased cardiac fibrosis, and cardiac dysfunction in twelve-week male diabetic Akita. Then, we analyzed the transcriptome levels in the heart. NGS analyses on Akita heart revealed 137 differentially expressed transcripts, where Bone Morphogenic Protein-10 (BMP10) was the most upregulated and hairy and enhancer of split-related (HELT) was the most downregulated gene. Moreover, twelve long non-coding RNAs (lncRNAs) were upregulated. The microarray analyses on Akita heart showed 351 differentially expressed transcripts, where vomeronasal-1 receptor-180 (Vmn1r180) was the most upregulated and WD Repeat Domain 83 Opposite Strand (WDR83OS) was the most downregulated gene. Further, miR-101c and H19 lncRNA were upregulated but Neat1 lncRNA was downregulated in Akita heart. Eleven common genes were upregulated in Akita heart in both NGS and microarray analyses. IPA analyses revealed the role of these differentially expressed genes in key signaling pathways involved in diabetic cardiomyopathy. Our results provide a platform to initiate focused future studies by targeting these genes and/or non-coding RNAs, which are differentially expressed in Akita hearts and are involved in diabetic cardiomyopathy.

Original languageEnglish (US)
Article numbere0182828
JournalPloS one
Volume12
Issue number8
DOIs
StatePublished - Aug 2017

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Gene Expression Profiling
Microarrays
transcriptomics
cardiomyopathy
heart
Diabetic Cardiomyopathies
Long Noncoding RNA
mice
Genes
heart failure
Transcriptome
transcriptome
Down-Regulation
Heart Failure
Microarray Analysis
Cardiomyopathies
genes
Untranslated RNA
Gene Targeting
gene targeting

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Cardiac transcriptome profiling of diabetic Akita mice using microarray and next generation sequencing. / Kesherwani, Varun; Shahshahan, Hamid R.; Mishra, Paras Kumar.

In: PloS one, Vol. 12, No. 8, e0182828, 08.2017.

Research output: Contribution to journalArticle

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