Blockade of Toll-like receptor 4 (TLR4) reduces oxidative stress and restores phospho-ERK1/2 levels in Leydig cells exposed to high glucose

Karpova, Tatiana; Oliveira, Amanda Almeida de; Naas, Huda; Priviero, Fernanda; Nunes, Kênia Pedrosa

doi:10.1016/j.lfs.2020.117365

Cited by 18 publications

(13 citation statements)

References 45 publications

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“… 61 In addition, the increased abundance of Escherichia coli ( E. coli ) in the microbiome of patients with type 2 diabetes increases the level of uric acid, leading to the generation of oxygen free radicals, causing neuronal cell apoptosis and extensive damage to retinal endothelial cells, and also promotes the onset of DR. 62 High glucose level could induce toll-like receptor (TLR-4) expression in retinal ganglion cells (RGCs), regulate its signaling pathways and increase the expression of inflammation cytokines such as TNF-α, IL-8, and NF-κB, and thus promote glycosylation enzyme activity, activate microglia, increase vascular permeability and generate neuronal damage, which ultimately exacerbate retinopathy. 63 , 64 …”

Section: Hypothesis That Gut Microbiota Cause Drmentioning

confidence: 99%

Recent Insights into the Role of Gut Microbiota in Diabetic Retinopathy

Jiao¹,

Yu²,

Yao³

et al. 2021

JIR

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The microbiome has become a hot issue in recent years. The composition, modification, alteration, and disturbance of gut microbiota were found to influence important physiological processes, including energy metabolism and microenvironmental homeostasis, and lead to various diseases, including obesity, type 2 diabetes mellitus and chronic kidney disease. Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus and one of the leading causes of blindness and vision impairment. The underlying mechanisms in DR pathogenesis remain limited. Recently, important insights have been made regarding possible connections between gut microbiome dysbiosis and ocular disease including DR, uveitis, glaucoma, and age-related macular degeneration, and the concept of a “microbiota–gut–retina axis” has been put forward. Hence, we reviewed current understanding of the relationship between DR and gut microbiota. We summarized potential pathophysiological mechanisms that contribute to the role of the gut microbiota on DR, including hyperglycemia, anti-diabetes drugs, microbial metabolites, and inflammatory properties. We aimed to find novel effective therapeutic options to prevent the onset and development of DR.

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Section: Hypothesis That Gut Microbiota Cause Drmentioning

confidence: 99%

Recent Insights into the Role of Gut Microbiota in Diabetic Retinopathy

Jiao¹,

Yu²,

Yao³

et al. 2021

JIR

View full text Add to dashboard Cite

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“…In a stage‐dependent manner, hyperglycemia resulted in abnormal spermatogenesis and sperm morphology, with a reduction in sperm count and motility (Kilarkaje et al, 2014). Another study has demonstrated that high glucose induces the expression inflammation‐mediating molecules, such as the expression TLR4 in Leydig cells (Karpova et al, 2020). This was exposing the germ and Leydig cells to the detrimental effect of radicals whereas treatment with antioxidants may result in lower level of malondialdehyde (MDA), protein carbonyl, greater level of glutathione (GSH) and recover of the antioxidant capacity, reflected by higher activity of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) (Khosravi et al, 2019).…”

Section: Resultsmentioning

confidence: 99%

Investigating the therapeutic options for diabetes‐associated male infertility as illustrated in animal experimental models

et al. 2022

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Diabetes is a rising global health concern and an increasingly common cause of male infertility. Although the definitive pathophysiological mechanisms underpinning the association between diabetes and infertility is unclear, there are several animal studies showing diabetes to be a detrimental factor on reproductive health through apoptosis, oxidative stress and impairment of steroidogenesis. Furthermore, as reflected in animal models, antidiabetic strategies and relevant treatments are beneficial in the management of infertile men with diabetes as the recovery of euglycemic status affects positively the spermatogenesis. However, the available data are still evolving and specific conclusion in human populations are not possible yet. In this review, we are discussing the current literature concerning the association of diabetes and male infertility, focusing on the therapeutic approach as illustrated in animals' models.

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“…miR504 mimic (sense:5′-AGACCCUGGUCUGCACUCUGUC-3′, antisense: 5′-CAGAGUGCAGACCAGGGUCUUU-3′), mi504 inhibitor (5′-GACAGAGUGCAGACCAGGGUCU-3′), miR935 mimic (sense:5′-CCAGUUACCGCUUCCGCUACCGC-3′, antisense: 5′-GGUAGCGGAAGCGGUAACUGGUU-3′), mi935 inhibitor (5′-GCGGUAGCGGAAGCGGUAACUGG-3′), mimicNC (sense:5′-UUCUCCGAACGUGUCACGUTT-3′, antisense: 5′-ACGUGACACGUUCGGAGAATT-3′) and inhibitor NC(5′-CAGUACUUUUGUGUAGUACAA-3′) were transfected at a final concentration of 50 nM for 24 h. Cell culture was maintained in DMEM (GIBCO, Grand Island, NY, USA) supplemented with 10% FBS (GIBCO,) in a humidified air incubator with 5% CO 2 at 37 °C. Leydig cells were exposed to normal (5 mM) or moderately high (15 mM) or high (30 mM) glucose concentrations for 48 h according to the previous study (Karpova et al 2020 ).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA regulation of the proliferation and apoptosis of Leydig cells in diabetes

Wei

et al. 2021

Mol Med

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Background The number of patients with diabetes is increasing worldwide. Diabetic testicular damage can cause spermiogenesis disorders and sexual dysfunction. We thus explored the role of miRNAs in diabetic testicular damage, and revealed that they could serve as effective prevention and treatment therapeutic targets. Methods Streptozotocin (STZ) was used to generate a rat model of type 2 diabetes. Rat testicular tissues were used for miRNA and mRNA sequencing. Through bioinformatics analysis, we constructed an miRNA–mRNA diabetic testicular damage regulatory network and screened for key miRNAs. We also used Leydig cells to generate a diabetic cell model and detected the downstream target genes of miRNAs, secretion of testosterone, and proliferation and apoptotic levels to elucidate the role and mechanism of the selected miRNAs in diabetic testicular damage. Results Using second-generation sequencing, we identified 19 differentially expressed miRNAs and 555 mRNAs in the testes of diabetic rats. Based on computational prediction of targets and negative regulation relationships, we constructed a miRNA–mRNA regulatory network, including 12 miRNAs and 215 mRNAs. KEGG enrichment analysis revealed that genes were more concentrated on the survival signalling pathway. Based on this, we screened 2 key miRNAs, miR-504 and miR-935. In vitro, glucose could induce an increase in miR-504 and miR-935, whereas a decrease in MEK5 and MEF2C in a dose-dependent manner. Overexpression of miR-504 and miR-935 led to the decreased expression of MEK5 and MEF2C, decreased proliferation rate of Leydig cells, increased apoptotic rate, and decreased secretion of testosterone. Whereas, knockdown of miR-504 and miR-935 displayed opposite tendencies. Conclusions miRNAs play important roles in diabetic testicular damage. miR-504 and miR-935 might regulate testicular damage through the classic survival pathway of MEK5-ERK5-MEF2C. Targeted inhibition of miR-504 and miR-935 could reverse the high-glucose-induced testicular complications, thus posing as a potential therapeutic approach in diabetic testicular injury.

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Blockade of Toll-like receptor 4 (TLR4) reduces oxidative stress and restores phospho-ERK1/2 levels in Leydig cells exposed to high glucose

Cited by 18 publications

References 45 publications

Recent Insights into the Role of Gut Microbiota in Diabetic Retinopathy

Recent Insights into the Role of Gut Microbiota in Diabetic Retinopathy

Investigating the therapeutic options for diabetes‐associated male infertility as illustrated in animal experimental models

MicroRNA regulation of the proliferation and apoptosis of Leydig cells in diabetes

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