MiR-451 antagonist protects against cardiac fibrosis in streptozotocin-induced diabetic mouse heart

Liang, Cui; Gao, Lu; Liu, Yuan; Yao, Rui; Li, Yapeng; Xiao, Lili; Wu, Leiming; Du, Binbin; Huang, Zhen; Zhang, Yanzhou

doi:10.1016/j.lfs.2019.02.059

Cited by 28 publications

(9 citation statements)

References 32 publications

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“…In particular, the presence of a high level of miR-216 in the apoptotic bodies of dying endothelial cells and high expression of miR-126 in serum suggest it as a potential biomarker for T2DM patients and can be used to monitor the development of different complications in diabetes (36). Nevertheless, the miR-451 antagonist has also been reported to protect against cardiac fibrosis in streptozotocin-induced diabetic mouse heart (37). While IFN-α is a pleiotropic cytokine that exerts contrasting injurious and conducive effects on T1DM, its production could be correlated with T1DM pathogenesis, which assists the regulation of established diabetes (38,39).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Overexpression of microRNA-216a-3p Accelerates the Inflammatory Response in Cardiomyocytes in Type 2 Diabetes Mellitus by Targeting IFN-α2

Liu

Liang

2020

Front. Endocrinol.

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Background: Type 2 diabetes mellitus (T2DM) is a chronic, hyperglycemia-associated, metabolic disorder. Heart disease is a major complication of T2DM. The present study aimed to explore the effects of miR-216a-3p on cardiomyocyte proliferation, apoptosis, and inflammation in T2DM through the Toll-like receptor (TLR) pathway involving interferon-α2 (IFN-α2) mediation.Methods: T2DM was induced in rats by a high-fat diet, in combination with an intraperitoneal injection of low-dose streptozotocin. ELISAs were conducted to measure inflammatory-related factors in serum. Next, isolated cardiomyocytes were used in loss- and gain-of-function experiments, followed by MTT and flow cytometry assays, conducted to evaluate cell proliferation, cell cycle, and apoptosis.Results: Our results revealed an increase in the inflammatory response in T2DM rat models, accompanied by significantly increased expression of miR-216a-3p and TLR pathway-related genes. However, a decrease in the expression of IFN-α2 was observed. Moreover, the presence of an miR-216a-3p inhibitor and si-IFN-α2 increased the expression of TLR pathway-related genes and cell apoptosis, whereas cell proliferation was significantly decreased in the cardiomyocytes.Conclusion: We found that in T2DM, miR-216a-3p inhibited the proliferation and enhanced the apoptosis of cardiomyocytes and generated an inflammatory response through activation of the TLR pathway and targeting of IFN-α2.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Overexpression of microRNA-216a-3p Accelerates the Inflammatory Response in Cardiomyocytes in Type 2 Diabetes Mellitus by Targeting IFN-α2

Liu

Liang

2020

Front. Endocrinol.

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“…Another proof of the oxidative stress-small RNAs-EndMT interconnection comes from a study investigating the activity of miR-451 (Ruknarong et al, 2021). The latter, previously described for its ability to induce EndMT in diabetic mouse heart (Liang et al, 2019), has been recently reported to be up-regulated in diabetic subjects with high oxidative stress. The association between miR-451 and oxidative stress has been further confirmed with the use of the antioxidant Vitamin C; indeed, Vitamin C administration in diabetic subjects decreased both the expression of miR-451 and ROS levels (Ruknarong et al, 2021).…”

Section: Potential Ros-endmt-small Rnas Interplay In Diabetes-associated Fibrotic Conditionsmentioning

confidence: 97%

“…Finally, a further TGF-β/SMAD pathway-mediated regulatory mechanism involves miR-451 whose effects on EndMT are AMPK-dependent. Indeed, miR451 knockdown in diabetic mouse hearts suppresses EndMT through the activation of AMPK, which in turn inhibits the TGF-β/SMAD pathway ( Liang et al, 2019 ). As previously mentioned, in addition to TGF-β/SMAD, other pathways underlie the pathophysiological events leading to cardiac fibrosis.…”

Section: Mirnas Regulation Of Dcm-associated Endmtmentioning

confidence: 99%

EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress

Giordo

Ahmed

Allam

et al. 2021

Front. Cell Dev. Biol.

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Diabetes-associated complications, such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis, the main consequences of long-term hyperglycemia, often lead to organ dysfunction, disability, and increased mortality. A common denominator of these complications is the myofibroblast-driven excessive deposition of extracellular matrix proteins. Although fibroblast appears to be the primary source of myofibroblasts, other cells, including endothelial cells, can generate myofibroblasts through a process known as endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their typical phenotype to acquire mesenchymal features, characterized by the development of invasive and migratory abilities as well as the expression of typical mesenchymal products such as α-smooth muscle actin and type I collagen. EndMT is involved in many chronic and fibrotic diseases and appears to be regulated by complex molecular mechanisms and different signaling pathways. Recent evidence suggests that small RNAs, in particular microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are crucial mediators of EndMT. Furthermore, EndMT and miRNAs are both affected by oxidative stress, another key player in the pathophysiology of diabetic fibrotic complications. In this review, we provide an overview of the primary redox signals underpinning the diabetic-associated fibrotic process. Then, we discuss the current knowledge on the role of small RNAs in the regulation of EndMT in diabetic retinopathy, nephropathy, cardiomyopathy, and atherosclerosis and highlight potential links between oxidative stress and the dyad small RNAs-EndMT in driving these pathological states.

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“…14,15 Deleterious miRNAs such as miR-208a, miR-451, miR-146a, and miR-200c and protective miRNAs such as miR-133a, miR-30c, miR-21, miR-22, and miR-181a have been found to contribute to diabetic cardiac injury. [16][17][18][19][20][21][22][23] These previous findings suggest that the manipulation of miRNAs may serve as a novel therapeutic approach for targeting heart diseases in diabetes. However, only a limited number of studies on the roles of miRNAs in mitochondrial biogenesis in DCM have been conducted.…”

Section: Introductionmentioning

confidence: 84%

“…One such example is of adverse cardiac remodeling in the diabetic myocardium . Deleterious miRNAs such as miR‐208a, miR‐451, miR‐146a, and miR‐200c and protective miRNAs such as miR‐133a, miR‐30c, miR‐21, miR‐22, and miR‐181a have been found to contribute to diabetic cardiac injury . These previous findings suggest that the manipulation of miRNAs may serve as a novel therapeutic approach for targeting heart diseases in diabetes.…”

Section: Introductionmentioning

confidence: 95%

MiR‐144 protects the heart from hyperglycemia‐induced injury by regulating mitochondrial biogenesis and cardiomyocyte apoptosis

Tao

Huang

et al. 2019

FASEB j.

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contributed equally to this work.Abbreviations: AMPK, adenosine monophosphate-activated protein kinase; ATP, adenosine triphosphate; A, atrial contraction; BSA, bovine serum albumin; CAD, coronary artery disease; DCM, diabetic cardiomyopathy; DMEM, Dulbecco's modified Eagle's medium; E, peak filling rates of the early filling phase; e', early diastolic lengthening mitral valve flow velocity; EF, ejection fraction; eNOs, endothelial NO synthase; FBS, fetal bovine serum; FS, left ventricular fractional shortening; Gated-MPI, Gated-myocardial perfusion imaging; HG, high glucose; LVDD, left ventricle diastolic dysfunction; LVIDd, left ventricular internal dimension-diastole; LVIDs, left ventricular internal dimension-systole; LV mass, left ventricular mass; miRNA, microRNA; mtDNA, mitochondrial DNA; NC, negative control; Nox, nicotinamide adenine dinucleotide phosphate oxidase; NRF1, nuclear respiratory factor 1; OXPHOS, oxidative phosphorylation; PAK, p21-activated protein kinase; PBD, p21-binding domain; PFA, paraformaldehyde; PGC-1α, peroxisome proliferator-activated receptor γ coactivator 1α; qRT-PCR, Quantitative real-time polymerase chain reactions; ROC, receiver-operator characteristic; ROS, reactive oxygen species; SIRT1, silent information regulator 1; SPF, specific pathogen-free; STZ, streptozotocin; TCA, , tricarboxylic acid; T2DM, type 2 diabetes; TFAM, mitochondrial transcription factor A; TEM, transmission electron microscope; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end labeling; VADT, veterans affairs diabetes trial; WGA, wheat germ agglutinin. AbstractSeveral lines of evidence have revealed the potential of microRNAs (miRNAs, miRs) as biomarkers for detecting diabetic cardiomyopathy, although their functions in hyperglycemic cardiac dysfunction are still lacking. In this study, mitochondrial biogenesis was markedly impaired induced by high glucose (HG), as evidenced by dysregulated mitochondrial structure, reduced mitochondrial DNA contents, and biogenesis-related mRNA levels, accompanied by increased cell apoptosis. MiR-144 was identified to be decreased in HG-induced cardiomyocytes and in streptozotocin (STZ)-challenged heart samples. Forced miR-144 expression enhanced mitochondrial biogenesis and suppressed cell apoptosis, while miR-144 inhibition exhibited the opposite results. Rac-1 was identified as a target gene of miR-144. Decreased Rac-1 levels activated AMPK phosphorylation and PGC-1α deacetylation, leading to increased mitochondrial biogenesis and reduced cell apoptosis. Importantly, the systemic neutralization of miR-144 attenuated mitochondrial disorder and ventricular dysfunction following STZ treatment. Additionally, plasma miR-144 decreased markedly in diabetic patients with cardiac dysfunction. The receiver-operator characteristic curve showed that plasma miR-144 could specifically predict diabetic patients developing cardiac dysfunction. In conclusion, this study provides strong 2174 |

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MiR-451 antagonist protects against cardiac fibrosis in streptozotocin-induced diabetic mouse heart

Cited by 28 publications

References 32 publications

RETRACTED: Overexpression of microRNA-216a-3p Accelerates the Inflammatory Response in Cardiomyocytes in Type 2 Diabetes Mellitus by Targeting IFN-α2

RETRACTED: Overexpression of microRNA-216a-3p Accelerates the Inflammatory Response in Cardiomyocytes in Type 2 Diabetes Mellitus by Targeting IFN-α2

EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress

MiR‐144 protects the heart from hyperglycemia‐induced injury by regulating mitochondrial biogenesis and cardiomyocyte apoptosis

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