<i>DUSP-1</i> gene expression is not regulated by promoter methylation in diabetes-associated cardiac hypertrophy

Singh, Gurdeep; Khanna, Sanskriti; Raut, Satish K; Sharma, Saurabh; Sharma, Rajni; Khullar, Madhu

doi:10.1177/1753944717704590

Cited by 12 publications

(9 citation statements)

References 23 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High DUSP1 expression can be found in several tissues, including the heart, lungs, and liver [21]. In the heart, DUSP1 regulates cardiac metabolism, and the inhibition of DUSP1 (or MKP1) was reported to induce cardiac hypertrophy in a transgenic mouse model [22]. In addition, a study by Weng et al reported that the expression of DUSP1 was low in the myocardium of a diabetic rat; this suggests that the abnormal expression of DUSP1 might involve the pathophysiology of diabetic cardiomyopathy [23].…”

Section: Introductionmentioning

confidence: 99%

MiR-32-5p influences high glucose-induced cardiac fibroblast proliferation and phenotypic alteration by inhibiting DUSP1

Shen

Xing

et al. 2019

BMC Molecular Biol

View full text Add to dashboard Cite

Background The current study aimed to investigate the effects of miR-32-5p on cardiac fibroblasts (CFs) that were induced with high levels of glucose; we also aimed to identify the potential mechanisms involved in the regulation of DUSP1 expression. Methods Human CFs were transfected with a miR-32-5p inhibitor or mimic and were treated with a normal concentration or a high concentration of glucose. Flow cytometry analysis was performed to identify cardiac fibroblasts by examining vimentin, fibronectin (FN) and α-actin expression in human CFs. qRT-PCR and western blot assays were performed to confirm the expression of miR-32-5p, DUSP1 and cardiac fibrosis relevant proteins. The proliferation of CFs was assessed by using MTT assay. An immunocytofluorescent staining assay was performed to determine the protein level of α-SMA and to investigate the degree of phenotypic changes in human CFs. The specific relationship between miR-32-5p and DUSP1 was investigated by a dual luciferase reporter assay. Cell apoptosis rates were measured with flow cytometry and the annexin V-FITC and propidine iodide (PI) staining method. Results A luciferase reporter assay indicated that miR-32-5p could directly target DUSP1. High glucose levels resulted in the overexpression of miR-32-5p, which downregulated DUSP1 expression. Both the upregulation of miR-32-5p and the downregulation of DUSP1 promoted cell apoptosis, proliferation and phenotypic changes in human CFs. Conclusions All findings in this study provide further evidence for the positive effects of miR-32-5p on cell proliferation and the phenotypic changes in CFs by inhibiting DUSP1 expression, and reveal that miR-32-5p could serve as prognostic diagnostic target for cardiac fibrosis. Electronic supplementary material The online version of this article (10.1186/s12867-019-0135-x) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

MiR-32-5p influences high glucose-induced cardiac fibroblast proliferation and phenotypic alteration by inhibiting DUSP1

Shen

Xing

et al. 2019

BMC Molecular Biol

View full text Add to dashboard Cite

show abstract

“…DCM is characterized by structural and functional abnormalities in the myocardium such as cardiac fibrosis, ventricular hypertrophy and heart failure . Several mechanisms have been implicated to be associated with the pathogenesis of DCM, including myocardial insulin resistance, cardiac inflammation, oxidative stress, interstitial fibrosis, cardiac cell death and apoptosis .…”

Section: Introductionmentioning

confidence: 99%

An Aza resveratrol–chalcone derivative 6b protects mice against diabetic cardiomyopathy by alleviating inflammation and oxidative stress

You

Qian

Sun

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

Inflammation and oxidative stress play a crucial role in the development of diabetic cardiomyopathy (DCM). We previously had synthesized an Aza resveratrol–chalcone derivative 6b, of which effectively suppressing lipopolysaccharide (LPS)‐induced inflammatory response in macrophages. This study aimed to investigate the potential protective effect of 6b on DCM and underlying mechanism. In H9c2 myocardial cells, 6b potently decreased high glucose (HG)‐induced cell fibrosis, hypertrophy and apoptosis, alleviating inflammatory response and oxidant stress. In STZ‐induced type 1 diabetic mice (STZ‐DM1), orally administration with 6b for 16 weeks significantly attenuated cardiac hypertrophy, apoptosis and fibrosis. The expression of inflammatory cytokines and oxidative stress biomarkers was also suppressed by 6b distinctly, without affecting blood glucose and body weight. The anti‐inflammatory and antioxidative activities of 6b were mechanistic associated with nuclear factor‐kappa B (NF‐κB) nucleus entry blockage and Nrf2 activation both in vitro and in vivo. The results indicated that 6b can be a promising cardioprotective agent in treatment of DCM via inhibiting inflammation and alleviating oxidative stress. This study also validated the important role of NF‐κB and Nrf2 taken in the pathogenesis of DCM, which could be therapeutic targets for diabetic comorbidities.

show abstract

“…18 It still remains a great challenge to explain the underlying mechanism involved in myocardial remodeling. It is well-known that the dual speci city phosphatases (DUSPs) family involved in the development of myocardial remodeling [19][20][21]. [19][20][21] However, the role of DUSPs varies under different stimulation and experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

Dual-Specificity Phosphatase 19 Alleviates Cardiac Hypertrophy Via Inhibiting ASK1 Phosphorylation

Jia

Liu

et al. 2022

SSRN Journal

View full text Add to dashboard Cite

DUSP-1 gene expression is not regulated by promoter methylation in diabetes-associated cardiac hypertrophy

Abstract: Methylation-mediated silencing of the DUSP-1 promoter does not appear to be associated with reduced expression, indicating the involvement of other factors in specific suppression of DUSP-1 in diabetes-associated cardiac hypertrophy.

Cited by 12 publications

References 23 publications

MiR-32-5p influences high glucose-induced cardiac fibroblast proliferation and phenotypic alteration by inhibiting DUSP1

MiR-32-5p influences high glucose-induced cardiac fibroblast proliferation and phenotypic alteration by inhibiting DUSP1

An Aza resveratrol–chalcone derivative 6b protects mice against diabetic cardiomyopathy by alleviating inflammation and oxidative stress

Dual-Specificity Phosphatase 19 Alleviates Cardiac Hypertrophy Via Inhibiting ASK1 Phosphorylation

Contact Info

Product

Resources

About