miR‐30c Mediates Upregulation of Cdc42 and Pak1 in Diabetic Cardiomyopathy

Raut, Satish K; Kumar, Akhilesh; Singh, Gurdeep; Nahar, Uma; Sharma, Vibhuti; Mittal, Anupam; Sharma, Rajni; Khullar, Madhu

doi:10.1111/1755-5922.12113

Cited by 58 publications

(46 citation statements)

References 30 publications

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“…Further investigation indicated that miR-30c possessed binding sites for the 3'-UTR and open reading frame (ORF) regions of Cdc42 and Pak1, and modulated Cdc42 and Pak1 expression levels in cardiomyocytes. In addition, miR-30c overexpression decreased HG-induced upregulation of Cdc42 and Pak1 and resulted in decreased expression levels of hypertrophic marker, atrial natriuretic peptide and a reduction in HG-treated cardiomyocyte cell size (35). These findings indicate that miR-30c exerts an anti-hypertrophic effect by inhibiting Cdc42 and Pak1 gene expression levels in DCM.…”

Section: Mir Involvement In the Pathogenesis Of Dcmmentioning

confidence: 73%

“…1. Furthermore, numerous studies have demonstrated that interventions with the expression levels of associated miRNs may improve the pathophysiological process of DCM, providing novel insights into targets for the prevention and treatment of DCM (28,29,34,35,45). However, those studies were limited to the expression changes of miRs in heart tissue samples.…”

Section: Resultsmentioning

confidence: 99%

“…p21-activated kinases (PAKs) and cell division control protein 42 homolog (Cdc42) are components of the PI3K/AKT signaling pathway, and PAKs are effectors of Cdc42. Myocardial Cdc42 and Pak1 mRNA and protein expression levels were found to be significantly increased in DCM rats with cardiac hypertrophy and in high glucose (HG)-treated cardiomyocytes, which was accompanied by a significant decrease in cardiac miR-30c expression levels in DCM rats (3.73-fold), patients with DCM (2.9-fold) and in HG-treated cardiomyocytes (3.5-fold) (35). Further investigation indicated that miR-30c possessed binding sites for the 3'-UTR and open reading frame (ORF) regions of Cdc42 and Pak1, and modulated Cdc42 and Pak1 expression levels in cardiomyocytes.…”

Section: Mir Involvement In the Pathogenesis Of Dcmmentioning

confidence: 99%

“…Cardiomyocyte hypertrophy is one of the distinct structural features of DCM. Studies have shown that various miRs were dysregulated and contributed to the pathogenesis of cardiomyocyte hypertrophy in DCM (29,(33)(34)(35)(36). miR-30c, miR-133a, miR-150 and miR-373 were found to be downregulated in the heart of DCM, while miR-451 was found to be upregulated (29,(33)(34)(35)(36).…”

Section: Mir Involvement In the Pathogenesis Of Dcmmentioning

confidence: 99%

“…Studies have shown that various miRs were dysregulated and contributed to the pathogenesis of cardiomyocyte hypertrophy in DCM (29,(33)(34)(35)(36). miR-30c, miR-133a, miR-150 and miR-373 were found to be downregulated in the heart of DCM, while miR-451 was found to be upregulated (29,(33)(34)(35)(36). miR-133 is abundantly expressed in heart tissue, and is known to regulate various physiological and pathophysiological events, including non-diabetic cardiac hypertrophy (37)(38)(39).…”

Section: Mir Involvement In the Pathogenesis Of Dcmmentioning

confidence: 99%

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Role of microRNAs in the pathogenesis of diabetic cardiomyopathy

Liu

2017

Biomedical Reports

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Abstract. The morbidity of diabetes mellitus has been increasing annually. As a progressive metabolic disorder, chronic complications occur in the late stage of diabetes. In addition, cardiovascular diseases account for the major cause of morbidity and mortality among the diabetic population worldwide. Diabetic cardiomyopathy (DCM) is a type of diabetic heart disease. Patients with DCM show symptoms and signs of heart failure while no specific cause, such as coronary disease, hypertension, alcohol consumption, or other structural heart diseases has been identified. The pathogenesis of DCM is complex and has not been well understood until recently. MicroRNAs (miRs) belong to a novel family of highly conserved, short, non-coding, single-stranded RNA molecules that regulate transcriptional and post-transcriptional gene expression. Furthermore, recent studies have demonstrated an association between miRs and DCM. In the current review, the role of miRs in the pathogenesis of DCM is summarized. It was concluded that miRs contribute to the regulation of cardiomyocyte hypertrophy, myocardial fibrosis, cardiomyocyte apoptosis, mitochondrial dysfunction, myocardial electrical remodeling, epigenetic modification and various other pathophysiological processes of DCM. These studies may provide novel insights into targets for prevention and treatment of the disease.

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Section: Mir Involvement In the Pathogenesis Of Dcmmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Section: Mir Involvement In the Pathogenesis Of Dcmmentioning

confidence: 99%

Section: Mir Involvement In the Pathogenesis Of Dcmmentioning

confidence: 99%

Section: Mir Involvement In the Pathogenesis Of Dcmmentioning

confidence: 99%

See 3 more Smart Citations

Role of microRNAs in the pathogenesis of diabetic cardiomyopathy

Liu

2017

Biomedical Reports

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Pathophysiological Fundamentals of Diabetic Cardiomyopathy

Bai

et al. 2017

Comprehensive Physiology

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Diabetic cardiomyopathy (DCM) was first recognized more than four decades ago and occurred independent of cardiovascular diseases or hypertension in both type 1 and type 2 diabetic patients. The exact mechanisms underlying this disease remain incompletely understood. Several pathophysiological bases responsible for DCM have been proposed, including the presence of hyperglycemia, nonenzymatic glycosylation of large molecules (e.g., proteins), energy metabolic disturbance, mitochondrial damage and dysfunction, impaired calcium handling, reactive oxygen species formation, inflammation, cardiac cell death, and cardiac hypertrophy and fibrosis, leading to impairment of cardiac contractile functions. Increasing evidence also indicates the phenomenon called "metabolic memory" for diabetes-induced cardiovascular complications, for which epigenetic modulation seemed to play an important role, suggesting that the aforementioned pathogenic bases may be regulated by epigenetic modification. Therefore, this review aims at briefly summarizing the current understanding of the pathophysiological bases for DCM. Although how epigenetic mechanisms play a role remains incompletely understood now, extensive clinical and experimental studies have implicated its importance in regulating the cardiac responses to diabetes, which are believed to shed insight into understanding of the pathophysiological and epigenetic mechanisms for the development of DCM and its possible prevention and/or therapy. © 2017 American Physiological Society. Compr Physiol 7:693-711, 2017.

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Epigenetics in Reactive and Reparative Cardiac Fibrogenesis: The Promise of Epigenetic Therapy

Ghosh

Rai

Flevaris

et al. 2017

Journal Cellular Physiology

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Epigenetic changes play a pivotal role in the development of a wide spectrum of human diseases including cardiovascular diseases, cancer, diabetes, and intellectual disabilities. Cardiac fibrogenesis is a common pathophysiological process seen during chronic and stress-induced accelerated cardiac aging. While adequate production of extracellular matrix (ECM) proteins is necessary for post-injury wound healing, excessive synthesis and accumulation of extracellular matrix protein in the stressed or injured hearts causes decreased or loss of lusitropy that leads to cardiac failure. This self-perpetuating deposition of collagen and other matrix proteins eventually alter cellular homeostasis; impair tissue elasticity and leads to multi-organ failure, as seen during pathogenesis of cardiovascular diseases, chronic kidney diseases, cirrhosis, idiopathic pulmonary fibrosis, and scleroderma. In the last 25 years, multiple studies have investigated the molecular basis of organ fibrosis and highlighted its multi-factorial genetic, epigenetic, and environmental regulation. In this minireview, we focus on five major epigenetic regulators and discuss their central role in cardiac fibrogenesis. Additionally, we compare and contrast the epigenetic regulation of hypertension-induced reactive fibrogenesis and myocardial infarction-induced reparative or replacement cardiac fibrogenesis. As microRNAs-one of the major epigenetic regulators-circulate in plasma, we also advocate their potential diagnostic role in cardiac fibrosis. Lastly, we discuss the evolution of novel epigenetic-regulating drugs and predict their clinical role in the suppression of pathological cardiac remodeling, cardiac aging, and heart failure. J. Cell. Physiol. 232: 1941-1956, 2017. © 2016 Wiley Periodicals, Inc.

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miR‐30c Mediates Upregulation of Cdc42 and Pak1 in Diabetic Cardiomyopathy

Cited by 58 publications

References 30 publications

Role of microRNAs in the pathogenesis of diabetic cardiomyopathy

Role of microRNAs in the pathogenesis of diabetic cardiomyopathy

Pathophysiological Fundamentals of Diabetic Cardiomyopathy

Epigenetics in Reactive and Reparative Cardiac Fibrogenesis: The Promise of Epigenetic Therapy

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