miR-181-5p attenuates neutrophilic inflammation in asthma by targeting DEK

Song, Yang; Jiang, Jingzhi; Piao, Yihua; Bai, Qiaoyun; Piao, Qinji; Li, Li; Xu, Chang; Liu, Hanye; Piao, Hongmei; Li, Liangchang; Yan, Guanghai

doi:10.1016/j.intimp.2022.109243

Cited by 9 publications

(4 citation statements)

References 33 publications

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“…66 Alternatively, miR-181a-5p may limit neutrophilic inflammation. 67 Two miRNAs, miR-181a-3p and miR-495-3p, showed increased expression in stroke participants versus controls at 15 days poststroke, but only in the validation cohort. MiR-181a-3p was associated with decreased cellular proliferation much like the parent strand miR-181a-5p described above.…”

Section: Brain-enriched Mirnasmentioning

confidence: 91%

Expansion of plasma MicroRNAs over the first month following human stroke

Edwardson,

Shivapurkar,

et al. 2023

J Cereb Blood Flow Metab

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Few have characterized miRNA expression during the transition from injury to neural repair and secondary neurodegeneration following stroke in humans. We compared expression of 754 miRNAs from plasma samples collected 5, 15, and 30 days post-ischemic stroke from a discovery cohort (n = 55) and 15-days post-ischemic stroke from a validation cohort (n = 48) to healthy control samples (n = 55 and 48 respectively) matched for age, sex, race and cardiovascular comorbidities using qRT-PCR. Eight miRNAs remained significantly altered across all time points in both cohorts including many described in acute stroke. The number of significantly dysregulated miRNAs more than doubled from post-stroke day 5 (19 miRNAs) to days 15 (50 miRNAs) and 30 (57 miRNAs). Twelve brain-enriched miRNAs were significantly altered at one or more time points (decreased expression, stroke versus controls: miR-107; increased expression: miR-99-5p, miR-127-3p, miR-128-3p, miR-181a-3p, miR-181a-5p, miR-382-5p, miR-433-3p, miR-491-5p, miR-495-3p, miR-874-3p, and miR-941). Many brain-enriched miRNAs were associated with apoptosis over the first month post-stroke whereas other miRNAs suggested a transition to synapse regulation and neuronal protection by day 30. These findings suggest that a program of decreased cellular proliferation may last at least 30 days post-stroke, and points to specific miRNAs that could contribute to neural repair in humans.

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Section: Brain-enriched Mirnasmentioning

confidence: 91%

Expansion of plasma MicroRNAs over the first month following human stroke

Edwardson,

Shivapurkar,

et al. 2023

J Cereb Blood Flow Metab

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“…The pro-inflammatory chemokine interleukin-8 (IL-8) induces monocyte-derived macrophages to secrete phosphorylated DEK, which can acts as a chemokine to attract neutrophils, CD8 + T lymphocytes, and natural killer cells ( 23 ). Our previous studies have demonstrated that DEK protein was highly expressed in asthma and DEK-targeting aptamer DTA-64 or miRNA-181b-5p inhibited airway inflammation and airway remodeling in asthma ( 24 , 25 ). Recently, Zhang et al.…”

Section: Introductionmentioning

confidence: 99%

DEK deficiency suppresses mitophagy to protect against house dust mite-induced asthma

Bai,

Liu,

Quan

et al. 2024

Front. Immunol.

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DEK protein is highly expressed in asthma. However, the mechanism of DEK on mitophagy in asthma has not been fully understood. This study aims to investigate the role and mechanism of DEK in asthmatic airway inflammation and in regulating PINK1-Parkin-mediated mitophagy, NLRP3 inflammasome activation, and apoptosis. PINK1-Parkin mitophagy, NLRP3 inflammasome, and apoptosis were examined after gene silencing or treatment with specific inhibitors (MitoTEMPO, MCC950, and Ac-DEVD-CHO) in house dust mite (HDM) or recombinant DEK (rmDEK)-induced WT and DEK-/- asthmatic mice and BEAS-2B cells. The regulatory role of DEK on ATAD3A was detected using ChIP-sequence and co-immunoprecipitation. rmDEK promoted eosinophil recruitment, and co-localization of TOM20 and LC3B, MFN1 and mitochondria, LC3B and VDAC, and ROS generation, reduced protein level of MnSOD in HDM induced-asthmatic mice. Moreover, rmDEK also increased DRP1 expression, PINK1-Parkin-mediated mitophagy, NLRP3 inflammasome activation, and apoptosis. These effects were partially reversed in DEK-/- mice. In BEAS-2B cells, siDEK diminished the Parkin, LC3B, and DRP1 translocation to mitochondria, mtROS, TOM20, and mtDNA. ChIP-sequence analysis showed that DEK was enriched on the ATAD3A promoter and could positively regulate ATAD3A expression. Additionally, ATAD3A was highly expressed in HDM-induced asthma models and interacted with DRP1, and siATAD3A could down-regulate DRP1 and mtDNA-mediated mitochondrial oxidative damage. Conclusively, DEK deficiency alleviates airway inflammation in asthma by down-regulating PINK1-Parkin mitophagy, NLRP3 inflammasome activation, and apoptosis. The mechanism may be through the DEK/ATAD3A/DRP1 signaling axis. Our findings may provide new potential therapeutic targets for asthma treatment.

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“…A wide range of posttranslational modifications influences multiple roles of DEK, mainly via decreasing its DNA binding capacity and allowing its secretion [12]. DEK is secreted passively from Tlymphocytes that undergo apoptosis and actively from immune cells and epithelial cells after IL-8 stimulation [10][11][12][13]. Secreted DEK may interact with heparin sulfate peptidoglycan receptors leading to entrance into the cell [10,14], or it may interact with the CXCR2 receptor and via Gαi signaling suppresses hematopoietic progenitor cell proliferation [15].…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, DEK-targeting aptamers reduce NETosis of the neutrophils in the JIA-mouse model [16]. In addition, human bronchial epithelial cells release DEK upon IL-8 stimulation, and supernatants of these cells, or rDEK alone, induce NETosis of human neutrophils in vitro, which is suppressed by overexpression of miR-181b-5p that directly targets and inhibits DEK mRNA expression [13].…”

Section: Introductionmentioning

confidence: 99%

NETosis Induced by Serum of Patients with COVID-19 is Reduced with Reparixin or Antibodies Against DEK and IL-8

Kilic

Yasar

Camci

et al. 2023

Preprint

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DEK locates in the nucleus of the cells or the cytoplasmic granules of neutrophils and plays different roles in cellular processes including NETosis, a suicide mechanism of neutrophils. Here we showed that the interaction of rDEK with CXCR2 leads to NETosis, which could be reduced by the CXCR1/CXCR2 inhibitor reparixin. We found that IL-8, IL-6, IL1-β, MPO, and CitH3 were increased whereas DEK was decreased in the serum of COVID-19 patients. Interestingly, reparixin or anti-DEK antibody reduced the NETosis induced by the serums of patients , suggesting that initial cytokine stimulation may further induce the release of DEK. Our results support the use of reparixin as a potential therapeutic strategy in COVID-19 and suggest that DEK-CXCR2 interaction plays a role in NETosis.

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miR-181-5p attenuates neutrophilic inflammation in asthma by targeting DEK

Cited by 9 publications

References 33 publications

Expansion of plasma MicroRNAs over the first month following human stroke

Expansion of plasma MicroRNAs over the first month following human stroke

DEK deficiency suppresses mitophagy to protect against house dust mite-induced asthma

NETosis Induced by Serum of Patients with COVID-19 is Reduced with Reparixin or Antibodies Against DEK and IL-8

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