MicroRNA-146a negatively regulates PTGS2 expression induced by Helicobacter pylori in human gastric epithelial cells

Liu, Zhen; Wang, Di; Hu, Yongliang; Zhou, Guoyong; Zhu, Chao-Hui; Qi, Yu; Ying-chun, Chi; Cao, Yingli; Jia, Chiyu; Zou, Quanming

doi:10.1007/s00535-012-0609-9

Cited by 34 publications

(25 citation statements)

References 27 publications

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“…We found that transfection of ECs with mimics of miR-374a and miR-568 significantly attenuated the 18% CS-and LPS-induced augmented PBEF/NAMPT mRNA and protein levels ( Figures 4A and 4B and 5A-5C). Although the exact mechanism by which miR-374a and miR-568 mimics alter PBEF/NAMPT expression is not known, our data support recent evidence that the majority of mammalian miRNAs directly target mRNA down-regulation via cleavage and degradation (52,53) or accelerated deadenylation of mRNAs (54,55).…”

Section: Discussionsupporting

confidence: 86%

Mechanical Stress Induces Pre–B-cell Colony-Enhancing Factor/NAMPT Expression via Epigenetic Regulation by miR-374a and miR-568 in Human Lung Endothelium

Adyshev

Elangovan

Moldobaeva

et al. 2014

Am J Respir Cell Mol Biol

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Increased lung vascular permeability and alveolar edema are cardinal features of inflammatory conditions such as acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). We previously demonstrated that pre-B-cell colony-enhancing factor (PBEF)/NAMPT, the proinflammatory cytokine encoded by NAMPT, participates in ARDS and VILI inflammatory syndromes. The present study evaluated posttranscriptional regulation of PBEF/NAMPT gene expression in human lung endothelium via 39-untranslated region (UTR) microRNA (miRNA) binding. In silico analysis identified hsa-miR-374a and hsa-miR-568 as potential miRNA candidates. Increased PBEF/NAMPT transcription (by RT-PCR) and expression (by Western blotting) induced by 18% cyclic stretch (CS) (2 h: 3.4 6 0.06 mRNA fold increase (FI); 10 h: 1.5 6 0.06 protein FI) and by LPS (4 h: 3.8 6 0.2 mRNA FI; 48 h: 2.6 6 0.2 protein FI) were significantly attenuated by transfection with mimics of hsa-miR-374a or hsa-miR-568 (40-60% reductions each). LPS and 18% CS increased the activity of a PBEF/NAMPT 39-UTR luciferase reporter (2.4-3.25 FI) with induction reduced by mimics of each miRNA (44-60% reduction). Specific miRNA inhibitors (antagomirs) for each PBEF/ NAMPT miRNA significantly increased the endogenous PBEF/ NAMPT mRNA (1.4-3.4 6 0.1 FI) and protein levels (1.2-1.4 6 0.1 FI) and 39-UTR luciferase activity (1.4-1.7 6 0.1 FI) compared with negative antagomir controls. Collectively, these data demonstrate that increased PBEF/NAMPT expression induced by bioactive agonists (i.e., excessive mechanical stress, LPS) involves epigenetic regulation with hsa-miR-374a and hsa-miR-568, representing novel therapeutic strategies to reduce inflammatory lung injury.

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Section: Discussionsupporting

confidence: 86%

Mechanical Stress Induces Pre–B-cell Colony-Enhancing Factor/NAMPT Expression via Epigenetic Regulation by miR-374a and miR-568 in Human Lung Endothelium

Adyshev

Elangovan

Moldobaeva

et al. 2014

Am J Respir Cell Mol Biol

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“…Furthermore, we found that transfection of ECs with miR-374a, miR-374b, miR-1290, and miR-520c-3p mimics significantly attenuated the 18% CS-, TNF-a-, and LPS-induced augmented nmMLCK mRNA level (Figure 4). Initial miRNA reports suggested that mammalian miRNAs function by translation repression of their target genes (46); however, recent evidence indicates that these miRNAs directly target mRNA downregulation via cleavage and degradation (47)(48)(49)(50) or accelerated deadenylation of mRNAs (51,52). Our data support these findings.…”

Section: Discussionsupporting

confidence: 83%

MicroRNA Regulation of Nonmuscle Myosin Light Chain Kinase Expression in Human Lung Endothelium

Adyshev

Moldobaeva

Mapes

et al. 2013

Am J Respir Cell Mol Biol

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Increased lung vascular permeability, the consequence of endothelial cell (EC) barrier dysfunction, is a cardinal feature of inflammatory conditions such as acute lung injury and sepsis and leads to lethal physiological dysfunction characterized by alveolar flooding, hypoxemia, and pulmonary edema. We previously demonstrated that the nonmuscle myosin light chain kinase isoform (nmMLCK) plays a key role in agonist-induced pulmonary EC barrier regulation. The present study evaluated posttranscriptional regulation of MYLK expression, the gene encoding nmMLCK, via 39 untranslated region (UTR) binding by microRNAs (miRNAs) with in silico analysis identifying hsa-miR-374a, hsa-miR-374b, hsa-miR-520c-3p, and hsa-miR-1290 as miRNA candidates. We identified increased MYLK gene transcription induced by TNF-a (24 h; 4.7 6 0.45 fold increase [FI]), LPS (4 h; 2.85 6 0.15 [FI]), and 18% cyclic stretch (24 h; 4.6 6 0.24 FI) that was attenuated by transfection of human lung ECs with mimics of hsa-miR-374a, hsa-miR-374b, hsa-miR-520c-3p, or hsa-miR-1290 (20-80% reductions by each miRNA). TNF-a, LPS, and 18% cyclic stretch each increased the activity of a MYLK 39UTR luciferase reporter (2.5-7.0 FI) with induction reduced by mimics of each miRNA (30-60% reduction). MiRNA inhibitors (antagomirs) for each MYLK miRNA significantly increased 39UTR luciferase activity (1.2-2.3 FI) and rescued the decreased MLCK-39UTR reporter activity produced by miRNA mimics (70-110% increases for each miRNA; P , 0.05). These data demonstrate that increased human lung EC expression of MYLK by bioactive agonists (excessive mechanical stress, LPS, TNF-a) is regulated in part by specific miRNAs (hsa-miR-374a, hsamiR-374b, hsa-miR-520c-3p, and hsa-miR-1290), representing a novel therapeutic strategy for reducing inflammatory lung injury.Keywords: miRNA; MLCK; acute lung injury; ventilator-induced lung injury; endothelial cellsThe pulmonary vascular endothelium serves as a semiselective barrier between circulating blood and surrounding tissues, with endothelial cell (EC) integrity being critical to tissue and organ function. Disruption of this vascular barrier induced by inflammatory agonists, such as IL-1b, TNF-a, and LPS, and by excessive mechanical stress, such as produced by shear stress or mechanical ventilation, leads to potentially lethal physiological dysfunction, such as hypoxemia and severe lung edema, which are hallmarks of acute inflammatory lung injury (ALI) (1-3). We previously demonstrated that MYLK, the gene encoding the critical cytoskeletal effector myosin light chain kinase (MLCK), is a compelling candidate gene in inflammatory lung injuries with critical modulation of vascular EC barrier integrity such as ALI and asthma (4-6). We cloned the full-length human MYLK gene encoding a novel nonmuscle MLCK isoform (nmMLCK) (210 kD) (7) and several nmMLCK splice variants that are also highly expressed in endothelium (8) and convincingly demonstrated nmMLCK as a multifunctional enzyme driving cytoskeletal participation in vascular barrier disrup...

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“…Scientists believe that better understanding of this complex network may help to explore the diagnostic and treatment methods. Recently, certain techniques such as gene chip and microarray analysis have been used to analyze global transcriptional changes in host genes in an attempt to describe the systemic response to H. pylori and to identify novel targets or biomarkers (2,3).…”

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confidence: 99%

Genome-Wide Analysis of Long Noncoding RNA Profile in Human Gastric Epithelial Cell Response to Helicobacter pylori

et al. 2015

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SUMMARY: Long noncoding RNAs (lncRNAs) are an important class of pervasive genes, and their misregulation has been shown in various types of diseases. However, the relationship between lncRNAs and the immune response to pathogen infection has been rarely reported. Helicobacter pylori is a major human pathogenic bacterium that causes gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. The regulatory mechanism of the H. pylori-induced immune response is not yet clear. In the present study, we identified nonoverlapping signatures of a small number of lncRNAs that were aberrantly expressed in H. pylori-infected gastric epithelial cells using microarray analysis followed by bioassays. From microarray data, we found that 23 lncRNAs were upregulated and 21 were downregulated. Five lncRNAs, XLOC_004562, XLOC_005912, XLOC_000620, XLOC_004122, and XLOC_014388, were further evaluated using quantitative reverse transcription-PCR, and the results matched well with microarray data. In addition, XLOC_004122 and XLOC_ 014388 were decreased in gastric mucosal tissues of H. pylori-positive patients. Differentially expressed lncRNAs may play a partial or key role in the immune response to H. pylori, and this may provide potential targets for the future treatment of H. pylori-related diseases.

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MicroRNA-146a negatively regulates PTGS2 expression induced by Helicobacter pylori in human gastric epithelial cells

Abstract: These results suggest that miR-146a may be involved in negatively regulating H. pylori-induced PTGS2 expression in human gastric epithelial cells.

Cited by 34 publications

References 27 publications

Mechanical Stress Induces Pre–B-cell Colony-Enhancing Factor/NAMPT Expression via Epigenetic Regulation by miR-374a and miR-568 in Human Lung Endothelium

Mechanical Stress Induces Pre–B-cell Colony-Enhancing Factor/NAMPT Expression via Epigenetic Regulation by miR-374a and miR-568 in Human Lung Endothelium

MicroRNA Regulation of Nonmuscle Myosin Light Chain Kinase Expression in Human Lung Endothelium

Genome-Wide Analysis of Long Noncoding RNA Profile in Human Gastric Epithelial Cell Response to Helicobacter pylori

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