Gadd45α: a novel diabetes-associated gene potentially linking diabetic cardiomyopathy and baroreflex dysfunction.

Both diabetic cardiomyopathy (DCM) and baroreflex dysfunction independently contribute to sudden cardiac death (SCD), however the inherent connections between them under diabetic state remains unclear. As microRNAs (miRNAs) have been reported to participate in various physiological and pathological...

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Autores principales: Ning Wang, Chao Yang, Fang Xie, Lihua Sun, Xiaolin Su, Ying Wang, Ran Wei, Rong Zhang, Xia Li, Baofeng Yang, Jing Ai
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:f6f13cda5fbf4c30a54e27ffab5b8d6e2021-11-18T08:06:23ZGadd45α: a novel diabetes-associated gene potentially linking diabetic cardiomyopathy and baroreflex dysfunction.1932-620310.1371/journal.pone.0049077https://doaj.org/article/f6f13cda5fbf4c30a54e27ffab5b8d6e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23227140/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Both diabetic cardiomyopathy (DCM) and baroreflex dysfunction independently contribute to sudden cardiac death (SCD), however the inherent connections between them under diabetic state remains unclear. As microRNAs (miRNAs) have been reported to participate in various physiological and pathological processes, we presume they may also be involved in DCM and DM-induced impairment of baroreflex sensitivity. Two sets of gene expression profiles data from streptozotocin (STZ)-induced diabetic heart and diabetic dorsal root ganglia (DDRG) were retrieved from GEO and ArrayExpress. Co-differentially-expressed genes in diabetic heart and DDRG were identified by t test and intersection analysis. Human Protein Reference Database (HPRD) was applied to find direct interacting proteins of Gadd45α. Differentially-expressed miRNAs in left ventricle from 4-week STZ-induced diabetic rats were screened by miRNA microarray. Expression of miR-499 and its regulating effect on Gadd45α were then verified by quantitative real-time PCR (qRT-PCR), western blot, computational predication, and dual-luciferase reporter analysis. Four co-differentially-expressed genes in DCM and DDRG were identified. Among these genes, Gadd45α has 16 direct interacting proteins and 11 of them are documentedly associated with DM. Accompanied with significantly increased miR-499 expression, Gadd45α expression was increased at mRNA level but decreased at protein level in both diabetic heart and nucleus ambiguous. Furthermore, miR-499 was confirmed negatively regulating Gadd45α by targeting its 3'UTR. Collectively, reduced Gadd45α protein expression by forced miR-499 expression indicated it's a diabetes-associated gene which might potentially be involved in both DCM and DM-induced baroreflex dysfunction.Ning WangChao YangFang XieLihua SunXiaolin SuYing WangRan WeiRong ZhangXia LiBaofeng YangJing AiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e49077 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ning Wang
Chao Yang
Fang Xie
Lihua Sun
Xiaolin Su
Ying Wang
Ran Wei
Rong Zhang
Xia Li
Baofeng Yang
Jing Ai
Gadd45α: a novel diabetes-associated gene potentially linking diabetic cardiomyopathy and baroreflex dysfunction.
description Both diabetic cardiomyopathy (DCM) and baroreflex dysfunction independently contribute to sudden cardiac death (SCD), however the inherent connections between them under diabetic state remains unclear. As microRNAs (miRNAs) have been reported to participate in various physiological and pathological processes, we presume they may also be involved in DCM and DM-induced impairment of baroreflex sensitivity. Two sets of gene expression profiles data from streptozotocin (STZ)-induced diabetic heart and diabetic dorsal root ganglia (DDRG) were retrieved from GEO and ArrayExpress. Co-differentially-expressed genes in diabetic heart and DDRG were identified by t test and intersection analysis. Human Protein Reference Database (HPRD) was applied to find direct interacting proteins of Gadd45α. Differentially-expressed miRNAs in left ventricle from 4-week STZ-induced diabetic rats were screened by miRNA microarray. Expression of miR-499 and its regulating effect on Gadd45α were then verified by quantitative real-time PCR (qRT-PCR), western blot, computational predication, and dual-luciferase reporter analysis. Four co-differentially-expressed genes in DCM and DDRG were identified. Among these genes, Gadd45α has 16 direct interacting proteins and 11 of them are documentedly associated with DM. Accompanied with significantly increased miR-499 expression, Gadd45α expression was increased at mRNA level but decreased at protein level in both diabetic heart and nucleus ambiguous. Furthermore, miR-499 was confirmed negatively regulating Gadd45α by targeting its 3'UTR. Collectively, reduced Gadd45α protein expression by forced miR-499 expression indicated it's a diabetes-associated gene which might potentially be involved in both DCM and DM-induced baroreflex dysfunction.
format article
author Ning Wang
Chao Yang
Fang Xie
Lihua Sun
Xiaolin Su
Ying Wang
Ran Wei
Rong Zhang
Xia Li
Baofeng Yang
Jing Ai
author_facet Ning Wang
Chao Yang
Fang Xie
Lihua Sun
Xiaolin Su
Ying Wang
Ran Wei
Rong Zhang
Xia Li
Baofeng Yang
Jing Ai
author_sort Ning Wang
title Gadd45α: a novel diabetes-associated gene potentially linking diabetic cardiomyopathy and baroreflex dysfunction.
title_short Gadd45α: a novel diabetes-associated gene potentially linking diabetic cardiomyopathy and baroreflex dysfunction.
title_full Gadd45α: a novel diabetes-associated gene potentially linking diabetic cardiomyopathy and baroreflex dysfunction.
title_fullStr Gadd45α: a novel diabetes-associated gene potentially linking diabetic cardiomyopathy and baroreflex dysfunction.
title_full_unstemmed Gadd45α: a novel diabetes-associated gene potentially linking diabetic cardiomyopathy and baroreflex dysfunction.
title_sort gadd45α: a novel diabetes-associated gene potentially linking diabetic cardiomyopathy and baroreflex dysfunction.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/f6f13cda5fbf4c30a54e27ffab5b8d6e
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