Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy

Zhao, Yang; Dong, Daoyin; Reece, E. Albert; Wang, Ashley R.; Yang, Peixin

doi:10.1016/j.ajog.2017.10.040

Cited by 42 publications

(34 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The results of the reporter luciferase assay suggest that several miRNAs including miR‐27a, miR‐142‐5p, miR‐153, and miR128 are direct modulators of the Nrf2 . On the other hand, these miRNAs have been related to human diseases such as cancer and diabetes, but whether these miRNAs play an active role in the pathogenesis of NAFLD remains to be determined. In the present study, we provided the evidence that among four miRNAs studied, miR‐27a, miR‐142‐5p expression in liver cells were consistently associated with NAFLD, both in animal model and in vitro.…”

Section: Discussionmentioning

confidence: 99%

Inhibiting miR‐27a and miR‐142‐5p attenuate nonalcoholic fatty liver disease by regulating Nrf2 signaling pathway

et al. 2019

View full text Add to dashboard Cite

Summary The gene Nrf2 (nuclear factor‐erythroid 2‐related factor 2) is the most important regulator of the cellular antioxidant system and its dysregulation has a role in the etiology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the association between Nrf2 targeted miRNAs (miR‐27a, miR‐142‐5p, miR‐153, and miR‐128) with lipid accumulation in vitro and in vivo models of NAFLD. We used two in vivo and in vitro models of NAFLD. The expression of the genes and miRNAs was assessed by real‐time PCR and the protein level was evaluated using western blot. To investigate the potential role of miRNAs in NAFLD, the inhibitors or mimics of the miR‐27a and miR‐142‐5p were transfected into HepG2 cells. The mRNA and protein levels of Nrf2 were significantly decreased in the liver of high fat diet‐fed mice as well as in HepG2 cells treated with high glucose (HG). Reduced expression of Nrf2 was associated with increased expression levels of miR‐27a and miR‐142‐5p in both models of NAFLD. HG‐induced triglyceride accumulation was attenuated by inhibition of miR‐27a or miR‐142‐5p in HepG2 cells. Overexpression of miR‐27a or miR‐142‐5p suppressed the expression of Nrf2 and its downstream antioxidant genes and increased production of reactive oxygen species, whereas inhibition of miR‐27a or miR‐142‐5p reversed these effects. In conclusion, the data of this study may suggest that miR‐27a and miR‐142‐5p are increased in NAFLD, where they suppress Nrf2 expression and contribute to the accumulation of lipids in the hepatocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibiting miR‐27a and miR‐142‐5p attenuate nonalcoholic fatty liver disease by regulating Nrf2 signaling pathway

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Various miRNAs including miR-7, miR27a, miR-34a and miR142-5p were reported to regulate the Nrf2-ARE pathway and glutathione homeostasis in the brain [36][37][38][39]. MiR-7 could increase the activity of Nrf2 and its downstream ARE, haeme oxygenase-1 (HO-1) and glutamate-cysteine ligase modifier subunit (GCLM), by repressing the inhibitor of Nrf2, Kelch-like ECH-associated protein 1 (Keap1) to exert cytoprotective effects in the brain [38].…”

Section: Discussionmentioning

confidence: 99%

The Differentially Expressed Circular RNAs in the Substantia Nigra and Corpus Striatum of Nrf2-Knockout Mice

Yang¹,

Zhang²,

Lin³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a protective role in both acute neuronal damage and chronic neurodegeneration-related oxidative stress. Circular RNAs (circRNAs) are involved with various diseases in the central nervous system (CNS). This study aimed to identify the key circRNAs involved in Nrf2-neuroprotection against oxidative stress. Methods: The differentially expressed circRNAs (DEcircRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice were identified by microarray analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of selected DEcircRNAs in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice. Based on our previous microarray analysis of the differentially expressed mRNAs (DEmRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice, the DEcircRNA-miRNA-DEmRNA interaction network was constructed. Functional annotation of DEmRNAs that shared the same binding miRNAs with DEcircRNAs was performed using gene ontology (GO) and pathway analyses. Results: A total of 65 and 150 significant DEcircRNAs were obtained in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, respectively, and seventeen shared DEcircRNAs were found in both these two tissues. The qRT-PCR results were generally consistent with the microarray results. The DEcircRNA-miRNA-DEmRNA interaction network and pathway analysis indicated that mmu_circRNA_34132, mmu_circRNA_017077 and mmu-circRNA-015216 might be involved with Nrf2-mediated neuroprotection against oxidative stress. Mmu_circRNA_015216 and mmu_circRNA_017077 might play roles in the Nrf2-related transcriptional misregulation and Nrf2-mediated processes of rheumatoid arthritis, respectively. In addition to these two processes, mmu_circRNA_34132 may be a potential regulator of Nrf2-mediated protection for diabetes mellitus and Nrf2-mediated defence against ROS in hearts. Conclusion: In conclusion, our study identified the key DEcircRNAs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, which might provide new clues for further exploring the mechanism of Nrf2-mediated neuroprotection against oxidative stress and other Nrf2-mediated processes.

show abstract

“…2). These results are in who found that upregulation of miR-27a in hyperglycemia 13,41,42 . Administration of QC in both pure and conjugated forms significantly decreased miR-27a expression to control level, suggesting the anti-oxidant effect of QC by miRNA regulation.…”

Section: Discussionmentioning

confidence: 60%

“…microRNA-27a is one of the redox-sensitive microRNAs or "redoximiRs" which plays a direct role in the downregulation of Nrf2 and modulation of Nrf2-driven antioxidant gene expression. It has been shown that enhancement of miR-27a leads to suppression of Nrf2 and further, repression of Nrf2-controlled antioxidant genes in diabetic embryopathy 13 . In addition, it has been reported that upregulation microRNAs cause neurodegeneration by reducing the levels of Nrf2 14 .…”

mentioning

confidence: 99%

Quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) increases Nrf2 expression via miR-27a mediation to prevent memory dysfunction in diabetic rats

Ebrahimpour

Shahidi

Abbasi

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Oxidative stress is one of the earliest defects involved in the development of diabetes-induced cognitive impairment. Nrf2 is the master regulator of the cellular antioxidant system can be regulated by some microRNAs. The study aimed to evaluate the effects of quercetin (QC) and quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) on Nrf2-controlled antioxidant genes through the redox-sensitive miR-27a. Expression levels of miR-27a, Nrf2, SOD1, GPX1, and CAT were measured by quantitative real-time PCR. Moreover, the oxidative stress parameters including total antioxidant capacity (TAC) and histological alterations were investigated. The expression level of miR-27a was significantly up-regulated in diabetic rats. While expression levels of Nrf2, SOD1, GPX1, and CAT were significantly down-regulated under diabetic condition. Interestingly, QCSPIONs decreased expression level of miR-27a and subsequently enhanced the expression levels of Nrf2, SOD1, and CAT to the control level. No significant difference was observed in the expression level of GPX1. Besides, QC in pure and especially conjugated form was able to normalize TAC and regenerate pathological lesions in STZ-diabetic rats. Our result demonstrates that QCSPIONs as an effective combined therapy can decrease miR-27a expression, which in turn increases the Nrf2 expression and responsive antioxidant genes, resulting in improvement of memory dysfunction in diabetic rats.

show abstract

Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy

Abstract: Our study demonstrates that maternal diabetes-induced oxidative stress increases miR-27a, which, in turn, suppresses nuclear factor erythroid 2-related factor 2 and its responsive antioxidant enzymes, resulting in diabetic embryopathy.

Cited by 42 publications

References 81 publications

Inhibiting miR‐27a and miR‐142‐5p attenuate nonalcoholic fatty liver disease by regulating Nrf2 signaling pathway

Inhibiting miR‐27a and miR‐142‐5p attenuate nonalcoholic fatty liver disease by regulating Nrf2 signaling pathway

The Differentially Expressed Circular RNAs in the Substantia Nigra and Corpus Striatum of Nrf2-Knockout Mice

Quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) increases Nrf2 expression via miR-27a mediation to prevent memory dysfunction in diabetic rats

Contact Info

Product

Resources

About