Emerging Roles of microRNAs as Biomarkers and Therapeutic Targets for Diabetic Neuropathy

Fan, Baoyan; Chopp, Michael; Zhang, Zheng Gang; Liu, Xian Shuang

doi:10.3389/fneur.2020.558758

Cited by 26 publications

(20 citation statements)

References 123 publications

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“…Moreover miRNAs can, either positively or negatively, regulate gene expression ( Catalanotto et al, 2016 ). As a result, they represent promising markers and druggable targets for many diseases, including diabetes ( Regazzi, 2018 ; Cao et al, 2019 ; Fan et al, 2020 ). An increasing amount of evidence also suggests that diabetes progression is linked to the alteration of miRNAs expression profiles; indeed, profibrotic miRNAs, such as miR-125b, let-7c, let-7g, miR-21, miR-30b, and miR-195 have been shown to be upregulated in EndMT.…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…As we know, RNAse leads to the destruction of miRNA, so it was loaded into extracellular vesicles to prevent its degradation. These exosome-loaded miRNAs impact physiological responses in beneficiary cells by controlling gene expression ( 95 ). Superoxide dismutase (SOD)-loaded polymersomes are highly beneficial in treating neuropathic pain, as they possess antioxidant action.…”

Section: Novel Approaches For Targeting the Dorsal Root Ganglion In M...mentioning

confidence: 99%

Novel Nanotechnological Approaches for Targeting Dorsal Root Ganglion (DRG) in Mitigating Diabetic Neuropathic Pain (DNP)

2022

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Diabetic neuropathy is the most entrenched complication of diabetes. Usually, it affects the distal foot and toes, which then gradually approaches the lower part of the legs. Diabetic foot ulcer (DFU) could be one of the worst complications of diabetes mellitus. Long-term diabetes leads to hyperglycemia, which is the utmost contributor to neuropathic pain. Hyperglycemia causing an upregulation of voltage-gated sodium channels in the dorsal root ganglion (DRG) was often observed in models of neuropathic pain. DRG opening frequency increases intracellular sodium ion levels, which further causes increased calcium channel opening and stimulates other pathways leading to diabetic peripheral neuropathy (DPN). Currently, pain due to diabetic neuropathy is managed via antidepressants, opioids, gamma-aminobutyric acid (GABA) analogs, and topical agents such as capsaicin. Despite the availability of various treatment strategies, the percentage of patients achieving adequate pain relief remains low. Many factors contribute to this condition, such as lack of specificity and adverse effects such as light-headedness, languidness, and multiple daily doses. Therefore, nanotechnology outperforms in every aspect, providing several benefits compared to traditional therapy such as site-specific and targeted drug delivery. Nanotechnology is the branch of science that deals with the development of nanoscale materials and products, even smaller than 100 nm. Carriers can improve their efficacy with reduced side effects by incorporating drugs into the novel delivery systems. Thus, the utilization of nanotechnological approaches such as nanoparticles, polymeric nanoparticles, inorganic nanoparticles, lipid nanoparticles, gene therapy (siRNA and miRNA), and extracellular vesicles can extensively contribute to relieving neuropathic pain.

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“…Models. Regarding diabetic neuropathy, in the last decade, very few studies have addressed miRNA expression in diabetic neuropathy with it being almost exclusively preclinical [34,35]. Studies in animal models of diabetes and diabetic neuropathy have documented changes in the expression of a few miRNAs in peripheral nerve structures as related to changes in key points of pathways known as or presumed to be involved in the diabetes-related pathogenesis of nerve damage, regeneration, and in pain generation [36][37][38][39][40][41][42][43] (Table 1).…”

Section: Mirna Expression and Diabetic Neuropathy In Animalmentioning

confidence: 99%

What Is in the Field for Genetics and Epigenetics of Diabetic Neuropathy: The Role of MicroRNAs

Spallone

Ciccacci

Latini

et al. 2021

Journal of Diabetes Research

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Despite the high prevalence of diabetic neuropathy, its early start, and its impact on quality of life and mortality, unresolved clinical issues persist in the field regarding its screening implementation, the understanding of its mechanisms, and the search for valid biomarkers, as well as disease-modifying treatment. Genetics may address these needs by providing genetic biomarkers of susceptibility, giving insights into pathogenesis, and shedding light on how to select possible responders to treatment. After a brief summary of recent studies on the genetics of diabetic neuropathy, the current review focused mainly on microRNAs (miRNAs), including the authors’ results in this field. It summarized the findings of animal and human studies that associate miRNAs with diabetic neuropathy and explored the possible pathogenetic meanings of these associations, in particular regarding miR-128a, miR-155a, and miR-499a, as well as their application for diabetic neuropathy screening. Moreover, from a genetic perspective, it examined new findings of polymorphisms of miRNA genes in diabetic neuropathy. It considered in more depth the pathogenetic implications for diabetic neuropathy of the polymorphism of MIR499A and the related changes in the downstream action of miR-499a, showing how epigenetic and genetic studies may provide insight into pathogenetic mechanisms like mitochondrial dysfunction. Finally, the concept and the data of genotype-phenotype association for polymorphism of miRNA genes were described. In conclusion, although at a very preliminary stage, the findings linking the genetics and epigenetics of miRNAs might contribute to the identification of exploratory risk biomarkers, a comprehensive definition of susceptibility to specific pathogenetic mechanisms, and the development of mechanism-based treatment of diabetic neuropathy, thus addressing the goals of genetic studies.

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Emerging Roles of microRNAs as Biomarkers and Therapeutic Targets for Diabetic Neuropathy

Cited by 26 publications

References 123 publications

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

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

Novel Nanotechnological Approaches for Targeting Dorsal Root Ganglion (DRG) in Mitigating Diabetic Neuropathic Pain (DNP)

What Is in the Field for Genetics and Epigenetics of Diabetic Neuropathy: The Role of MicroRNAs

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