Differential Expression of Dicer, miRNAs, and Inflammatory Markers in Diabetic Ins2+/- Akita Hearts

Vishalakshi Chavali, Suresh C. Tyagi, Paras Kumar Mishra

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Diabetic cardiomyopathy is a leading cause of morbidity and mortality, and Insulin2 mutant (Ins2+/-) Akita is a genetic mice model of diabetes relevant to humans. Dicer, miRNAs, and inflammatory cytokines are associated with heart failure. However, the differential expression of miRNAs, dicer, and inflammatory molecules are not clear in diabetic cardiomyopathy of Akita. We measured the levels of miRNAs, dicer, pro-inflammatory tumor necrosis factor alpha (TNFα), and anti-inflammatory interleukin 10 (IL-10) in C57BL/6J (WT) and Akita hearts. The results revealed increased heart to body weight ratio and robust expression of brain natriuretic peptide (BNP: a hypertrophy marker) suggesting cardiac hypertrophy in Akita. The multiplex RT-PCR, qPCR, and immunoblotting showed up regulation of dicer, whereas miRNA array elicited spread down regulation of miRNAs in Akita including dramatic down regulation of let-7a, miR-130, miR-142-3p, miR-148, miR-338, miR-345-3p, miR-384-3p, miR-433, miR-450, miR-451, miR-455, miR-494, miR-499, miR-500, miR-542-3p, miR-744, and miR-872. Conversely, miR-295 is induced in Akita. Cardiac TNFα is upregulated at mRNA (RT-PCR and qPCR), protein (immunoblotting), and cellular (immunohistochemistry and confocal microscopy) levels, and is robust in hypertrophic cardiomyocytes suggesting direct association of TNFα with hypertrophy. Contrary to TNFα, cardiac IL-10 is downregulated in Akita. In conclusion, induction of dicer and TNFα, and attenuation of IL-10 and majority of miRNA are associated with cardiomyopathy in Akita and could be used for putative therapeutic target for heart failure in diabetics.

Original languageEnglish (US)
Pages (from-to)25-35
Number of pages11
JournalCell Biochemistry and Biophysics
Volume68
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint

MicroRNAs
Tumor Necrosis Factor-alpha
Diabetic Cardiomyopathies
Interleukin-10
Down-Regulation
Immunoblotting
Hypertrophy
Heart Failure
Heart Neoplasms
Confocal microscopy
Brain Natriuretic Peptide
Multiplex Polymerase Chain Reaction
Genetic Models
Cardiomegaly
Medical problems
Cardiomyopathies
Cardiac Myocytes
Confocal Microscopy
Anti-Inflammatory Agents
Up-Regulation

Keywords

  • BNP
  • Diabetes
  • Heart failure
  • Hypertrophy
  • IL-10
  • TNFα

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Differential Expression of Dicer, miRNAs, and Inflammatory Markers in Diabetic Ins2+/- Akita Hearts. / Chavali, Vishalakshi; Tyagi, Suresh C.; Mishra, Paras Kumar.

In: Cell Biochemistry and Biophysics, Vol. 68, No. 1, 01.01.2014, p. 25-35.

Research output: Contribution to journalArticle

@article{f1caebf507e74c519a635f66e7679528,
title = "Differential Expression of Dicer, miRNAs, and Inflammatory Markers in Diabetic Ins2+/- Akita Hearts",
abstract = "Diabetic cardiomyopathy is a leading cause of morbidity and mortality, and Insulin2 mutant (Ins2+/-) Akita is a genetic mice model of diabetes relevant to humans. Dicer, miRNAs, and inflammatory cytokines are associated with heart failure. However, the differential expression of miRNAs, dicer, and inflammatory molecules are not clear in diabetic cardiomyopathy of Akita. We measured the levels of miRNAs, dicer, pro-inflammatory tumor necrosis factor alpha (TNFα), and anti-inflammatory interleukin 10 (IL-10) in C57BL/6J (WT) and Akita hearts. The results revealed increased heart to body weight ratio and robust expression of brain natriuretic peptide (BNP: a hypertrophy marker) suggesting cardiac hypertrophy in Akita. The multiplex RT-PCR, qPCR, and immunoblotting showed up regulation of dicer, whereas miRNA array elicited spread down regulation of miRNAs in Akita including dramatic down regulation of let-7a, miR-130, miR-142-3p, miR-148, miR-338, miR-345-3p, miR-384-3p, miR-433, miR-450, miR-451, miR-455, miR-494, miR-499, miR-500, miR-542-3p, miR-744, and miR-872. Conversely, miR-295 is induced in Akita. Cardiac TNFα is upregulated at mRNA (RT-PCR and qPCR), protein (immunoblotting), and cellular (immunohistochemistry and confocal microscopy) levels, and is robust in hypertrophic cardiomyocytes suggesting direct association of TNFα with hypertrophy. Contrary to TNFα, cardiac IL-10 is downregulated in Akita. In conclusion, induction of dicer and TNFα, and attenuation of IL-10 and majority of miRNA are associated with cardiomyopathy in Akita and could be used for putative therapeutic target for heart failure in diabetics.",
keywords = "BNP, Diabetes, Heart failure, Hypertrophy, IL-10, TNFα",
author = "Vishalakshi Chavali and Tyagi, {Suresh C.} and Mishra, {Paras Kumar}",
year = "2014",
month = "1",
day = "1",
doi = "10.1007/s12013-013-9679-4",
language = "English (US)",
volume = "68",
pages = "25--35",
journal = "Cell Biochemistry and Biophysics",
issn = "1085-9195",
publisher = "Humana Press",
number = "1",

}

TY - JOUR

T1 - Differential Expression of Dicer, miRNAs, and Inflammatory Markers in Diabetic Ins2+/- Akita Hearts

AU - Chavali, Vishalakshi

AU - Tyagi, Suresh C.

AU - Mishra, Paras Kumar

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Diabetic cardiomyopathy is a leading cause of morbidity and mortality, and Insulin2 mutant (Ins2+/-) Akita is a genetic mice model of diabetes relevant to humans. Dicer, miRNAs, and inflammatory cytokines are associated with heart failure. However, the differential expression of miRNAs, dicer, and inflammatory molecules are not clear in diabetic cardiomyopathy of Akita. We measured the levels of miRNAs, dicer, pro-inflammatory tumor necrosis factor alpha (TNFα), and anti-inflammatory interleukin 10 (IL-10) in C57BL/6J (WT) and Akita hearts. The results revealed increased heart to body weight ratio and robust expression of brain natriuretic peptide (BNP: a hypertrophy marker) suggesting cardiac hypertrophy in Akita. The multiplex RT-PCR, qPCR, and immunoblotting showed up regulation of dicer, whereas miRNA array elicited spread down regulation of miRNAs in Akita including dramatic down regulation of let-7a, miR-130, miR-142-3p, miR-148, miR-338, miR-345-3p, miR-384-3p, miR-433, miR-450, miR-451, miR-455, miR-494, miR-499, miR-500, miR-542-3p, miR-744, and miR-872. Conversely, miR-295 is induced in Akita. Cardiac TNFα is upregulated at mRNA (RT-PCR and qPCR), protein (immunoblotting), and cellular (immunohistochemistry and confocal microscopy) levels, and is robust in hypertrophic cardiomyocytes suggesting direct association of TNFα with hypertrophy. Contrary to TNFα, cardiac IL-10 is downregulated in Akita. In conclusion, induction of dicer and TNFα, and attenuation of IL-10 and majority of miRNA are associated with cardiomyopathy in Akita and could be used for putative therapeutic target for heart failure in diabetics.

AB - Diabetic cardiomyopathy is a leading cause of morbidity and mortality, and Insulin2 mutant (Ins2+/-) Akita is a genetic mice model of diabetes relevant to humans. Dicer, miRNAs, and inflammatory cytokines are associated with heart failure. However, the differential expression of miRNAs, dicer, and inflammatory molecules are not clear in diabetic cardiomyopathy of Akita. We measured the levels of miRNAs, dicer, pro-inflammatory tumor necrosis factor alpha (TNFα), and anti-inflammatory interleukin 10 (IL-10) in C57BL/6J (WT) and Akita hearts. The results revealed increased heart to body weight ratio and robust expression of brain natriuretic peptide (BNP: a hypertrophy marker) suggesting cardiac hypertrophy in Akita. The multiplex RT-PCR, qPCR, and immunoblotting showed up regulation of dicer, whereas miRNA array elicited spread down regulation of miRNAs in Akita including dramatic down regulation of let-7a, miR-130, miR-142-3p, miR-148, miR-338, miR-345-3p, miR-384-3p, miR-433, miR-450, miR-451, miR-455, miR-494, miR-499, miR-500, miR-542-3p, miR-744, and miR-872. Conversely, miR-295 is induced in Akita. Cardiac TNFα is upregulated at mRNA (RT-PCR and qPCR), protein (immunoblotting), and cellular (immunohistochemistry and confocal microscopy) levels, and is robust in hypertrophic cardiomyocytes suggesting direct association of TNFα with hypertrophy. Contrary to TNFα, cardiac IL-10 is downregulated in Akita. In conclusion, induction of dicer and TNFα, and attenuation of IL-10 and majority of miRNA are associated with cardiomyopathy in Akita and could be used for putative therapeutic target for heart failure in diabetics.

KW - BNP

KW - Diabetes

KW - Heart failure

KW - Hypertrophy

KW - IL-10

KW - TNFα

UR - http://www.scopus.com/inward/record.url?scp=84891612323&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891612323&partnerID=8YFLogxK

U2 - 10.1007/s12013-013-9679-4

DO - 10.1007/s12013-013-9679-4

M3 - Article

C2 - 23797610

AN - SCOPUS:84891612323

VL - 68

SP - 25

EP - 35

JO - Cell Biochemistry and Biophysics

JF - Cell Biochemistry and Biophysics

SN - 1085-9195

IS - 1

ER -