NFE2/miR-423-5p/TFF1 axis regulates high glucose-induced apoptosis in retinal pigment epithelial cells

Xiao, Qing; Zhao, Yihang; Xu, Jia; Li, Wenjie; Chen, Yu; Sun, Hong-Jing

doi:10.1186/s12860-019-0223-2

Cited by 24 publications

(21 citation statements)

References 28 publications

(33 reference statements)

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“…Mounting evidence supported the view that nuclear factor NF-κB is a transcription factor with multiple regulatory functions in cells (Xia et al 2014). Reports have demonstrated previously that the activity of NF-κB is closely related to DR and inhibition of NF-κB signaling can protect against HG-induced injury of RPE cells (Xiao et al 2019;Zhang et al 2019c). In addition, NLRP3 inflammasome pathway was reported to participate in the progress of DR (Hao et al 2019).…”

Section: Discussionmentioning

confidence: 87%

HDAC6 inhibitor Cay10603 inhibits high glucose-induced oxidative stress, inflammation and apoptosis in retinal pigment epithelial cells via regulating NF-κB and NLRP3 inflammasome pathway

Yang

Li²,

Zhou³

et al. 2020

gpb

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The present study aimed to investigate the effects of histone deacetylase 6 (HDAC6) inhibitor Cay10603 (Cay) on high glucose (HG)-stimulated human retinal pigment epithelium (RPE) cells and its underlying mechanisms. ARPE-19 cells were cultured under normal glucose (NG) or high glucose (HG) conditions. The results revealed that HDAC6 was upregulated in HG-stimulated ARPE-19 cells. Cay treatment caused a decrease in intracellular reactive oxygen species (ROS). The levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were reduced accompanied by increase in the activities of superoxide dismutase (SOD) and catalase (CAT) after treatment with Cay. Besides, Cay decreased the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and monocyte chemoattractant protein-1 (MCP-1) in supernatant. Meanwhile, the apoptotic rate in Cay-treated ARPE-19 cells notably reduced, coupled with an upregulation in Bcl-2 expression and a downregulation in cleaved caspase-3 and cleaved caspase-9 expression. Cay decreased the expression of phospho (p)-NF-κB p65, p-IκB-α, NLRP3, cleaved caspase-1 and ASC while increased the expression of NF-κB p65 (cytoplasm). Taken together, these findings demonstrated that Cay suppressed HG-induced oxidative stress, inflammation and apoptosis via regulating NF-κB and NLRP3 inflammasome pathway in HG-induced ARPE-19 cells, suggesting that Cay might be a therapeutic agent for the treatment of diabetic retinopathy.

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Section: Discussionmentioning

confidence: 87%

HDAC6 inhibitor Cay10603 inhibits high glucose-induced oxidative stress, inflammation and apoptosis in retinal pigment epithelial cells via regulating NF-κB and NLRP3 inflammasome pathway

Yang

Li²,

Zhou³

et al. 2020

gpb

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“…However, the role of METTL3 in the regulation of diabetes associated diseases is controversial [6,9], and the association between METTL3 and DR pathogenesis is still largely unknown. In addition, retinal pigment epithelium (RPE) cells were the main cells of the retina and widely used as an in vitro cellular model for DR research [10], hence, the RPE cell line ARPE-19 was selected in this study according to the previous publication [11].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8

Fan

et al. 2020

Aging

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Methyltransferase-like protein 3 (METTL3) regulates multiple cell functions and diseases by modulating N 6methyladenosine (m 6 A) modifications. However, it is still unclear whether METTL3 involves in the pathogenesis of diabetic retinopathy (DR). In the present study, we found that high-glucose inhibited RPE cell proliferation, promoted cell apoptosis and pyroptosis in a time-dependent manner. In addition, both METTL3 mRNA and miR-25-3p were low-expressed in the peripheral venous blood samples of diabetes mellitus (DM) patients compared to normal volunteers, and high-glucose inhibited METTL3 and miR-25-3p expressions in RPE cells. As expected, upregulation of METTL3 and miR-25-3p alleviated the cytotoxic effects of high-glucose on RPE cells, and knockdown of METTL3 and miR-25-3p had opposite effects. Additionally, METTL3 overexpression increased miR-25-3p levels in RPE cells in a microprocessor protein DGCR8-dependent manner, and miR-25-3p ablation abrogated the effects of overexpressed METTL3 on cell functions in high-glucose treated RPE cells. Furthermore, PTEN could be negatively regulated by miR-25-3p, and overexpression of METTL3 increased phosphorylated Akt (p-Akt) levels by targeting miR-25-3p/PTEN axis. Consistently, upregulation of PTEN abrogated the protective effects of METTL3 overexpression on RPE cells treated with high-glucose. Collectively, METTL3 rescued cell viability in highglucose treated RPE cells by targeting miR-25-3p/PTEN/Akt signaling cascade.

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“…While there is little additional evidence of a role for this miRNA in bone, it has also been linked to regulation of apoptosis in cardiomyocytes (Zhu and Lu 2019), kidney cells (Yuan et al 2017), retinal pigment epithelial cells (Q. Xiao et al 2019), and colon cancer cells (Jia et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNAs associated with bone mineral density in healthy adult baboons

Quillen

Foster

Sheldrake

et al. 2021

Preprint

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MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and circulate in the blood, making them attractive biomarkers of disease state for tissues like bone that are challenging to interrogate directly. Here we report on five miRNAs - miR-197-3p, miR-320a, miR-320b, miR-331-5p, and miR-423-5p - that are associated with bone mineral density (BMD) in 147 healthy adult baboons. These baboons range in age from 15 to 25 years (45 to 75 human equivalent years) and were 65% female with a broad range of BMDs including a minority of osteopenic individuals. miRNAs were generated via RNA sequencing from buffy coats collected at necropsy and areal BMD evaluated via DXA of the lumbar vertebrae post-mortem. Differential expression analysis controlled for the underlying pedigree structure of these animals to account for genetic variation which may be driving miRNA abundance and BMD values. While many of these miRNAs have been associated with risk of human osteoporosis, this finding is of interest because the cohort represent a model of normal aging and bone metabolism rather than a disease cohort. The replication of miRNA associations with osteoporosis or other bone metabolic disorders in animals with healthy BMD suggests an overlap in normal variation and disease states. We suggest that these miRNAs are involved in the regulation of cellular proliferation, apoptosis, and protein composition in the extracellular matrix throughout life. However, age-related dysregulation of these systems may lead to disease causing associations of the miRNAs among individuals with clinically defined disease.

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NFE2/miR-423-5p/TFF1 axis regulates high glucose-induced apoptosis in retinal pigment epithelial cells

Cited by 24 publications

References 28 publications

HDAC6 inhibitor Cay10603 inhibits high glucose-induced oxidative stress, inflammation and apoptosis in retinal pigment epithelial cells via regulating NF-κB and NLRP3 inflammasome pathway

HDAC6 inhibitor Cay10603 inhibits high glucose-induced oxidative stress, inflammation and apoptosis in retinal pigment epithelial cells via regulating NF-κB and NLRP3 inflammasome pathway

Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8

Circulating miRNAs associated with bone mineral density in healthy adult baboons

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