Relationship of miRNA-146a to systemic lupus erythematosus

Fan, Yihua; Ji, Yue; Wang, Xuyan; Hu, Jingyi; Zhang, Qiang; Xu, Jingyu; Liu, Wei; Wang, Aihua

doi:10.1097/md.0000000000022444

Cited by 7 publications

(6 citation statements)

References 26 publications

(26 reference statements)

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“…So, exploring abnormal expression molecules of CD4+ T Journal of Immunology Research lymphocytes in SLE patients may provide reliable targets for the diagnosis, efficacy, and prognosis evaluation of SLE and is also crucial for inhibiting SLE apoptosis and alleviating related cellular dysfunction. Numerous studies have shown that the abnormal miRNA expression is involved in the nosogenesis of SLE [40,41]. Along with the development of miRNA panels, miRNAs have been a research hotspot in the diagnostic area, but the therapeutic market that is driven primarily by antagomiR and miRNA mimic products is underdeveloped.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-137 Facilitates CD4+ T Cell Pyroptosis in Systemic Lupus Erythematosus via Stimulating AMPK Pathway

Gong

Wei

et al. 2023

Journal of Immunology Research

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Objective. From the pathogenic mechanism point of view, systemic lupus erythematosus (SLE) features prominently in T lymphocyte apoptosis. Yet the regulatory mechanism underlying SLE cell apoptosis remains to be explored. This research intends to clarify the role played by miR-137 in SLE and the underlying mechanisms. Methods. Twenty SLE patients (SLE group) and twenty healthy controls (control group) were selected, from whom peripheral blood CD4+ T cells were isolated via magnetic-activated cell sorting. Reverse transcription-polymerase chain reaction (RT-PCR) quantified miR-137 and AMP-activated protein kinase (AMPK) in CD4+ T cells. Further, transfection of miR-137 mimics and inhibitors into CD4+ T cells was carried out to alter miR levels. Levels of pyroptosis, apoptosis, and inflammatory- and pyroptosis-related proteins were determined through PI staining, flow cytometry, and Western blotting, respectively. A luciferase reporter gene assay identified the targeting relation between miR-137 and AMPK. Results. SLE patients showed downregulated miR-137 and upregulated AMPK in CD4+ T cells than controls. miR-137 upregulation by miR-137 mimic transfection inhibited Jurkat cell pyroptosis and apoptosis at both mRNA and protein levels and suppressed NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome activity and pyroptosis-related protein gasdermin D (GSDMD), while miR-137 inhibitor transfection contributed to completely opposite effects. miR-137 directly targeted AMPK, as indicated by the luciferase reporter gene assay. Furthermore, miR-137 inhibitor intervention induced healthy CD4+ T cell pyroptosis and apoptosis via mediating AMPK, whereas miR-137 mimic transfection into CD4+ T cells of SLE patients leads to opposite results. Conclusion. Upregulating miR-137 inhibits CD4+ T cell pyroptosis in SLE patients by modulating the AMPK pathway, suggesting the potential diagnostic and therapeutic role of miR-137 in SLE.

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Section: Discussionmentioning

confidence: 99%

Downregulation of miR-137 Facilitates CD4+ T Cell Pyroptosis in Systemic Lupus Erythematosus via Stimulating AMPK Pathway

Gong

Wei

et al. 2023

Journal of Immunology Research

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“…In agreement with our study, the study found a reverse correlation between type 1 interferon and SLE disease activity ( 14 ). In addition, recent meta-analyses showed that miR146a expression is associated with SLE risk and there were further differences in the expression of miR146a in Asian versus Caucasian populations ( 61 , 62 ). These differences in the expression level could be due to sample size, medications and active versus inactive disease status in SLE patients.…”

Section: Discussionmentioning

confidence: 99%

Identification and Contribution of Inflammation-Induced Novel MicroRNA in the Pathogenesis of Systemic Lupus Erythematosus

2022

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Recently microRNAs (miRNAs) have been recognized as powerful regulators of many genes and pathways involved in the pathogenesis of inflammatory diseases including Systemic Lupus Erythematosus (SLE). SLE is an autoimmune disease characterized by production of various autoantibodies, inflammatory immune cells, and dysregulation of epigenetic changes. Several candidate miRNAs regulating inflammation and autoimmunity in SLE are described. In this study, we found significant increases in the expression of miR21, miR25, and miR186 in peripheral blood mononuclear cells (PBMCs) of SLE patients compared to healthy controls. However, miR146a was significantly decreased in SLE patients compared to healthy controls and was negatively correlated with plasma estradiol levels and with SLE disease activity scores (SLEDAI). We also found that protein levels of IL-12 and IL-21 were significantly increased in SLE patients as compared to healthy controls. Further, our data shows that protein levels of IL-12 were positively correlated with miR21 expression and protein levels of IL-21 positively correlated with miR25 and miR186 expression in SLE patients. In addition, we found that levels of miR21, miR25, and miR186 positively correlated with SLEDAI and miR146a was negatively correlated in SLE patients. Thus, our data shows a dynamic interplay between disease pathogenesis and miRNA expression. This study has translational potential and may identify novel therapeutic targets in patients with SLE.

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“…Zeng et al confirmed the roles of miR‐371b‐5p and miR‐5100 in the serum of patients with SLE 10 . Fang and colleagues have reported the relationship between miR‐146a and SLE 11 . Furthermore, miR‐153‐3p has been reported to induce immune dysregulation by inhibiting PELI1 expression in patients with SLE, 12 which indicates that miR‐153‐3p may be a new therapeutic target for the treatment of LN.…”

Section: Introductionmentioning

confidence: 88%

“… 10 Fang and colleagues have reported the relationship between miR‐146a and SLE. 11 Furthermore, miR‐153‐3p has been reported to induce immune dysregulation by inhibiting PELI1 expression in patients with SLE, 12 which indicates that miR‐153‐3p may be a new therapeutic target for the treatment of LN. However, the roles and molecular mechanism of miR‐153‐3p in LN remain unclear.…”

Section: Introductionmentioning

confidence: 99%

LncRNA TUG1 relieves renal mesangial cell injury by modulating the miR‐153‐3p/Bcl‐2 axis in lupus nephritis

Liu

Zhang

Zhong

2023

Immunity Inflam & Disease

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Background Lupus nephritis (LN) is one of the most common and serious complications of systemic lupus erythematosus. Our experiments aimed to evaluate the molecular mechanisms of long noncoding RNA (lncRNA) TUG1 in a human renal mesangial cell (HRMC) model of LN. Methods Cells were treated with lipopolysaccharide (LPS) to induce inflammatory damage. StarBase, TargetScan, and a luciferase reporter assay were used to predict and confirm the interactions between lncRNA TUG1, miR‐153‐3p, and Bcl‐2. We determined the lncRNA TUG1 and miR‐153‐3p levels in LPS‐induced HRMCs using quantitative reverse transcription PCR (RT‐qPCR). MTT and flow cytometry analyses were used to detect HRMC proliferation and apoptosis, respectively. In addition, the expression of the apoptosis‐related proteins Bax and Bcl‐2 was evaluated using western blot analysis and RT‐qPCR. Lastly, the secretion of inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) was assessed using ELISA. Results miR‐153‐3p directly targeted lncRNA TUG1. The level of lncRNA TUG1 was remarkably lower and miR‐153‐3p expression was markedly higher in LPS‐treated HRMCs than in untreated cells. Transfection with TUG1‐plasmid relieved LPS‐induced HRMC injury, as evidenced by increased cell viability, inhibited apoptotic cells, reduced Bax expression, increased Bcl‐2 level, and reduced secretion of inflammatory cytokines. Importantly, these findings were reversed by miR‐153‐3p mimic. We also found that miR‐153‐3p directly targeted Bcl‐2 and negatively regulated Bcl‐2 expression in HRMCs. In addition, our findings suggest that miR‐153‐3p inhibitor relieved LPS‐induced HRMC injury via the upregulation of Bcl‐2. Conclusion lncRNA TUG1 alleviated LPS‐induced HRMC injury through regulation of the miR‐153‐3p/Bcl‐2 axis in LN.

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Relationship of miRNA-146a to systemic lupus erythematosus

Abstract: Supplemental Digital Content is available in the text

Cited by 7 publications

References 26 publications

Downregulation of miR-137 Facilitates CD4+ T Cell Pyroptosis in Systemic Lupus Erythematosus via Stimulating AMPK Pathway

Downregulation of miR-137 Facilitates CD4+ T Cell Pyroptosis in Systemic Lupus Erythematosus via Stimulating AMPK Pathway

Identification and Contribution of Inflammation-Induced Novel MicroRNA in the Pathogenesis of Systemic Lupus Erythematosus

LncRNA TUG1 relieves renal mesangial cell injury by modulating the miR‐153‐3p/Bcl‐2 axis in lupus nephritis

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