Dexmedetomidine attenuates lipopolysaccharide induced acute lung injury by targeting NLRP3 via miR‐381

Zhang, Yong; Wang, Xuan; Liu, Zhaoguo; Lan, Yu

doi:10.1002/jbt.22211

Cited by 33 publications

(19 citation statements)

References 33 publications

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“…ETS2 is a target of miR-381-3p, and the MAPK/miR-381 axis is involved in epithelial-mesenchymal transition in lung cancer 11 . More importantly, miR-381 is involved in the treatment of lipopolysaccharide (LPS)-induced acute lung injury by dexmedetomidine 12 . The same study also predicted that miR-381-3p was regulated by long non-coding RNA (lncRNA) Kcnq1 opposite strand/antisense transcript 1 (Kcnq1ot1) through competitive binding.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Kcnq1ot1/miR-381-3p/ETS2 Axis Regulates Inflammation in Mouse Models of Acute Respiratory Distress Syndrome

Jiang

Zhu

et al. 2020

Molecular Therapy - Nucleic Acids

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Inflammatory mediators play a key role in the pathogenesis of acute respiratory distress syndrome (ARDS). In this study, we aimed to explore the involvement of the Kcnq1 opposite strand/antisense transcript 1 (Kcnq1ot1)/miR-381-3p/E26 transformation-specific proto-oncogene 2 (ETS2) axis in inflammation of lipopolysaccharide (LPS)-induced ARDS. Microarray analysis revealed ETS2 as an upregulated gene in ARDS. Then, a LPS-induced ARDS mouse model was constructed, with a series of gain- or loss-of-function experiments conducted to evaluate the lung function and neutrophil extracellular trap (NET) formation in lung tissue and determine the neutrophil number, myeloperoxidase (MPO) activity, and inflammatory factor levels in bronchoalveolar lavage fluid (BALF). As the results revealed, downregulated expression of ETS2 resulted in improved lung function, decreased NETs, MPO activity, and levels of interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α), as well as increased IL-10 level. Then, the assays of dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and RNA pull-down were performed to validate that Kcnq1ot1 promoted ETS2 expression by competitively binding to miR-381-3p. Meanwhile, it was also found that Kcnq1ot1 silencing reversed the promotive effect of EST2 on ARDS. Our results provide evidence that Kcnq1ot1 silencing may reduce the inflammatory response in LPS-induced ARDS via inhibition of miR-381-30-dependent ETS2, thereby presenting new molecular understanding for the development of ARDS.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Kcnq1ot1/miR-381-3p/ETS2 Axis Regulates Inflammation in Mouse Models of Acute Respiratory Distress Syndrome

Jiang

Zhu

et al. 2020

Molecular Therapy - Nucleic Acids

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“…mir-381 has been reported to be dysregulated in various cancers (20)(21)(22), but few studies have focused on the role of mir-381 in cHd. a recent study demonstrated that overexpression of mir-381 in raW264.7 cell lines decreased the concentrations of il-1β and TnF-α (42). in addition, mir-381 can reduce inflammation and the infiltration of macrophages by targeting high-mobility group box 1 mrna (43).…”

Section: Discussionmentioning

confidence: 97%

Protective effect of microRNA‑381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4

Huang

Hong

et al. 2020

Mol Med Report

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coronary heart disease (cHd) is the leading cause of human morbidity and mortality worldwide. Microrna (mirna) profiling is an innovative method of identifying biomarkers for many diseases and may be a powerful tool in the diagnosis and treatment of cHd. The present study aimed to analyze the effects of miRNA (miR)-381 on the inflammatory damage of endothelial cells during cHd. a total of 21 patients with cHd and 21 healthy control patients were enrolled in this study. reverse transcription-quantitative PCR, western blotting and immunofluorescence assays were conducted to examine the expression levels of mir-381, c-X-c chemokine receptor type 4 (cXcr4), Bcl-2, Bax, cleaved-caspases-3 and-9, p38, erK1/2 and JnK. cell Counting Kit-8, EdU and flow cytometry experiments were performed to evaluate cell proliferation and apoptosis. an ELISA was adopted to determine the expressions of inflammatory factors (interleukins-8,-6 and-1β, and tumor necrosis factor-α). in addition, a dual-luciferase reporter assay was used to determine the relationship between mir-381 and cXcr4. decreased mir-381 expression and increased cXcr4 expression in the plasma were observed in the cHd group compared with the normal group, which indicated a negative relationship between mir-381 and cXcr4. overexpression of mir-381 significantly promoted the proliferation and inhibited the apoptosis of oxidized low-density lipoprotein (oX-ldl)-induced human umbilical vein endothelial cells (HuVecs) through mitogen-activated protein kinase pathway by targeting and inhibiting cXcr4. Furthermore, overexpression of miR-381 reduced the release of inflammatory factors in oX-ldl-induced HuVecs. By contrast, reduced expression of mir-381 exerted the opposite effects, which were subsequently reversed by silencing cXcr4 expression. results from the present study indicated that mir-381 was a cHd-related factor that may serve as a potential molecular target for cHd treatment.

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“…Moreover, Dex attenuated pancreatic inflammatory response in mice with pancreatitis by reduction in NLRP3 activation [16]. In lipopolysaccharide-induced acute lung injury, Dex inhibited NLRP3 activation through the up-regulation of miR-381 and miR-381-mediated degeneration of NLRP3 [17]. Lv et al [18] reported that Dex promotes liver regeneration in mice after 70% partial hepatectomy by suppressing NLRP3 inflammasome and not TLR4/NF-κB, since NLRP3 inhibition is associated with better liver regeneration and liver function recovery, while NF-κB inhibition conversely diminished liver regeneration.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine exerts dual effects on human annulus fibrosus chondrocytes depending on the oxidative stress status

Zhou

Sheng

et al. 2019

Bioscience Reports

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Dexmedetomidine (Dex) is an anesthetic widely used in lumbar discectomy, but its effect on chondrocytes remains unclear. Dex is speculated to promote cartilage degeneration by activating α-2 adrenergic receptor. However, the antioxidative and anti-inflammatory effects of Dex implied the potential chondrocyte protective effect under stress conditions. The present study aimed to determine the effect of Dex on chondrocytes under non-stress and stress conditions. Chondrocytes were isolated from human annulus fibrosus (AF) tissues and oxidative stress was induced by treatment with 1 mM hydrogen peroxide (H2O2). Chondrocytes were treated with Dex alone or in combination with H2O2. Treatment with Dex alone decreased mRNA expression of COL2A1 and increased that of MMP-3 and MMP-13, thus contributing to cartilage degeneration. However, Dex prevented H2O2-induced death and degeneration of chondrocytes partly by enhancing antioxidant capacity. Mechanistically, Dex attenuated H2O2-mediated activation of NF-κB and NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), both of which play key roles in inflammation and inflammatory damage. Dex inactivated NLRP3 through the suppression of NF-κB and JNK signals. Co-treatment with Dex and H2O2 increased protein level of XIAP (X-linked inhibitor-of-apoptosis, an anti-apoptosis protein), compared with H2O2 treatment alone. H2O2 treatment increased the expression of neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) that is a ubiquitin ligase targeting XIAP. However, Dex decreased the amount of NEDD4 adhering to XIAP, thus protecting XIAP protein from NEDD4-mediated ubiquitination and degradation. Given that surgery inevitably causes oxidative stress and inflammation, the protective effect of Dex on chondrocytes during oxidative stress is noteworthy and warrants further study.

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Dexmedetomidine attenuates lipopolysaccharide induced acute lung injury by targeting NLRP3 via miR‐381

Cited by 33 publications

References 33 publications

RETRACTED: Kcnq1ot1/miR-381-3p/ETS2 Axis Regulates Inflammation in Mouse Models of Acute Respiratory Distress Syndrome

RETRACTED: Kcnq1ot1/miR-381-3p/ETS2 Axis Regulates Inflammation in Mouse Models of Acute Respiratory Distress Syndrome

Protective effect of microRNA‑381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4

Dexmedetomidine exerts dual effects on human annulus fibrosus chondrocytes depending on the oxidative stress status

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