Investigating microRNAs in diabetic cardiomyopathy as tools for early detection and therapeutics

Mathur, Priyanka; Saxena, Sharad

doi:10.1007/s11010-022-04473-6

Cited by 3 publications

(5 citation statements)

References 60 publications

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“…There are many studies on the role of miR-503-5p in different cancers, but few studies have examined its role in DM and its related complications. In diabetic cardiomyopathy and foot syndrome, the expression of miR-503-5p is significantly upregulated 14 , 15 . Contrary to previous studies, this project shows that miR-503-5p expression is down regulated in DPN.…”

Section: Discussionmentioning

confidence: 99%

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MiR-503-5p alleviates peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 to inhibit astrocyte activation

Guo,

Zeng,

Zhuang

et al. 2024

Sci Rep

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Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that causes peripheral and autonomic nervous system dysfunction. Dysregulation of miRNAs plays a crucial role in DPN development. However, the role of miR-503-5p in DPN remains unknown. Herein, T2DM mice (db/db) were used as a DPN model in vivo, and astrocytes isolated from db/db mice were induced with high glucose levels as a DPN model in vitro. MiR-503-5p expression was analyzed using qRT-PCR. GFAP, MCP-1, and SEPT9 protein levels were analyzed using western blotting and immunofluorescence. Luciferase assays were performed to investigate the interaction between miR-503-5p and SEPT9. We found that miR-503-5p expression decreased in the spinal cord of DPN model mice and astrocytes treated with high glucose (HG). The db/db mice displayed higher body weight and blood glucose, lower mechanical withdrawal threshold and thermal withdrawal latency, and higher GFAP and MCP-1 protein levels than db/m mice. However, tail vein injection of agomiR-503-5p remarkably reversed these parameters, whereas antigomiR-503-5p enhanced them. HG markedly facilitated GFAP and MCP-1 protein expression in astrocytes, whereas miR-503-5p mimic or inhibitor transfection markedly blocked or elevated GFAP and MCP-1 protein expression, respectively, in astrocytes with HG. SEPT9 was a target of miR-503-5p. In addition, SEPT9 protein levels were found to be elevated in db/db mice and astrocytes treated with HG. Treatment with agomiR-503-5p and miR-503-5p mimic was able to reduce SEPT9 protein levels, whereas treatment with antigomiR-503-5p and miR-503-5p inhibitor led to inhibition of the protein. Furthermore, SEPT9 overexpression suppressed the depressing effect of miR-503-5p overexpression in astrocytes subjected to HG doses. In conclusion, miR-503-5p was found to alleviate peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 expression.

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Section: Discussionmentioning

confidence: 99%

“…miR-503-5p also plays an important role in the development of diabetic complications. In diabetic cardiomyopathy and foot syndrome, the expression of miR-503-5p is significantly upregulated 14 , 15 . In diabetic nephropathy, miR-503-5p enhances endoplasmic reticulum stress and cell apoptosis by downregulating BCL-2 16 .…”

Section: Introductionmentioning

confidence: 99%

MiR-503-5p alleviates peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 to inhibit astrocyte activation

Guo,

Zeng,

Zhuang

et al. 2024

Sci Rep

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“…It is also associated with mitochondrial dysfunction [58]. In addition, mitochondrial dysfunction contributes greatly to age-dependent IR [59] and induces diabetic microvascular (cardiomyopathy, nephropathy, retinopathy, and neuropathy) [60][61][62][63] and macrovascular (myocardial ischemia) [64] complications. Therefore, mitochondrial quality control is a promising intervention for managing T2D and obesity.…”

Section: Mitochondrial Dysfunction In Diabetes and Obesitymentioning

confidence: 99%

Mitochondrial transplantation: opportunities and challenges in the treatment of obesity, diabetes, and nonalcoholic fatty liver disease

et al. 2022

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Metabolic diseases, including obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD), are rising in both incidence and prevalence and remain a major global health and socioeconomic burden in the twenty-first century. Despite an increasing understanding of these diseases, the lack of effective treatments remains an ongoing challenge. Mitochondria are key players in intracellular energy production, calcium homeostasis, signaling, and apoptosis. Emerging evidence shows that mitochondrial dysfunction participates in the pathogeneses of metabolic diseases. Exogenous supplementation with healthy mitochondria is emerging as a promising therapeutic approach to treating these diseases. This article reviews recent advances in the use of mitochondrial transplantation therapy (MRT) in such treatment.

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“…MiRNAs are composed of approximately 22 nucleotide sequence, and regulate the expression of target genes at the post‐transcriptional levels via binding to the untranslated regions (UTRs) of complementary message RNAs 13 . Several studies have verified that the differential expression of miRNAs in myocardium are involved in DCM in either patients or animal models with DM 14–17 . Recently, we screened the expression profiles of miRNAs in myocardium from DCM mice, and found that miR‐185‐5p, one of the differentially expressed miRNAs, was markedly down‐regulated in DCM mice (Figure 2A).…”

Section: Introductionmentioning

confidence: 99%

“… 13 Several studies have verified that the differential expression of miRNAs in myocardium are involved in DCM in either patients or animal models with DM. 14 , 15 , 16 , 17 Recently, we screened the expression profiles of miRNAs in myocardium from DCM mice, and found that miR‐185‐5p, one of the differentially expressed miRNAs, was markedly down‐regulated in DCM mice (Figure 2A ). The miRNA candidate target mRNAs were predicted by miRDB database ( http://mirdb.org/miRDB/ ), and RhoA was shown to be a target gene of miR‐185‐5p, which were verified by NCBI ( http://www.ncbi.nlm.nih.gov/ ).…”

Section: Introductionmentioning

confidence: 99%

MALAT1/miR‐185‐5p mediated high glucose‐induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway

Wang

Yuan

et al. 2023

J Cellular Molecular Medi

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To explore the underlying mechanism of lncRNA MALAT1 in the pathogenesis of diabetic cardiomyopathy (DCM). DCM models were confirmed in db/db mice. MiRNAs in myocardium were detected by miRNA sequencing. The interactions of miR‐185‐5p with MALAT1 and RhoA were validated by dual‐luciferase reporter assays. Primary neonatal cardiomyocytes were cultured with 5.5 or 30 mmol/L D‐glucose (HG) in the presence or absence of MALAT1‐shRNA and fasudil, a ROCK inhibitor. MALAT1 and miR‐185‐5p expression were determined by real‐time quantitative PCR. The apoptotic cardiomyocytes were evaluated using flow cytometry and TUNEL staining. SOD activity and MDA contents were measured. The ROCK activity, phosphorylation of Drp1S616, mitofusin 2 and apoptosis‐related proteins were analysed by Western blotting. Mitochondrial membrane potential was examined by JC‐1. MALAT1 was significantly up‐regulated while miR‐185‐5p was down‐regulated in myocardium of db/db mice and HG‐induced cardiomyocytes. MALAT1 regulated RhoA/ROCK pathway via sponging miR‐185‐5p in cardiomyocytes in HG. Knockdown of MALAT1 and fasudil all inhibited HG‐induced oxidative stress, and alleviated imbalance of mitochondrial dynamics and mitochondrial dysfunction, accompanied by reduced cardiomyocyte apoptosis. MALAT1 activated the RhoA/ROCK pathway via sponging miR‐185‐5p and mediated HG‐induced oxidative stress, mitochondrial damage and apoptosis of cardiomyocytes in mice.

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Investigating microRNAs in diabetic cardiomyopathy as tools for early detection and therapeutics

Cited by 3 publications

References 60 publications

MiR-503-5p alleviates peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 to inhibit astrocyte activation

MiR-503-5p alleviates peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 to inhibit astrocyte activation

Mitochondrial transplantation: opportunities and challenges in the treatment of obesity, diabetes, and nonalcoholic fatty liver disease

MALAT1/miR‐185‐5p mediated high glucose‐induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway

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