Mechanical stress induces pre-B-cell colony-enhancing factor/NAMPT expression via epigenetic regulation by miR-374a and miR-568 in human lung endothelium.

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 3'-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 ± 0.06 mRNA fold increase (FI); 10 h: 1.5 ± 0.06 protein FI) and by LPS (4 h: 3.8 ± 0.2 mRNA FI; 48 h: 2.6 ± 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 3'-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 ± 0.1 FI) and protein levels (1.2-1.4 ± 0.1 FI) and 3'-UTR luciferase activity (1.4-1.7 ± 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.

[1]  M. Balaan,et al.  Acute Respiratory Distress Syndrome , 2016, Critical care nursing quarterly.

[2]  Y. Suárez,et al.  MicroRNAs as pharmacological targets in endothelial cell function and dysfunction. , 2013, Pharmacological research.

[3]  Brandon Mapes,et al.  MicroRNA regulation of nonmuscle myosin light chain kinase expression in human lung endothelium. , 2013, American journal of respiratory cell and molecular biology.

[4]  B. Fisslthaler,et al.  AMP-Activated Protein Kinase Regulates Endothelial Cell Angiotensin-Converting Enzyme Expression via p53 and the Post-Transcriptional Regulation of microRNA-143/145 , 2013, Circulation research.

[5]  A. Noël,et al.  MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines , 2013, Cell Death and Disease.

[6]  Jianwei Jiao,et al.  The role of microRNAs in neural stem cells and neurogenesis. , 2013, Journal of genetics and genomics = Yi chuan xue bao.

[7]  R. Ranjha,et al.  Micro-RNAs in inflammatory diseases and as a link between inflammation and cancer , 2013, Inflammation Research.

[8]  M. Stoffel,et al.  Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b , 2013, Nature.

[9]  Sue Fletcher,et al.  Regulation of eukaryotic gene expression by the untranslated gene regions and other non-coding elements , 2012, Cellular and Molecular Life Sciences.

[10]  Lin Zhang,et al.  Lin-28 Homologue A (LIN28A) Promotes Cell Cycle Progression via Regulation of Cyclin-dependent Kinase 2 (CDK2), Cyclin D1 (CCND1), and Cell Division Cycle 25 Homolog A (CDC25A) Expression in Cancer* , 2012, The Journal of Biological Chemistry.

[11]  S. Persengiev.  miRNAs at the crossroad between hematopoietic malignancies and autoimmune pathogenesis. , 2012, Discovery medicine.

[12]  R. Neumann,et al.  Unraveling the Global microRNAome Responses to Ionizing Radiation in Human Embryonic Stem Cells , 2012, PloS one.

[13]  A. Tijsen,et al.  Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? , 2012, Circulation research.

[14]  Li-San Wang,et al.  The microRNA miR-34 modulates aging and neurodegeneration in Drosophila , 2012, Nature.

[15]  Zhen Liu,et al.  MicroRNA-146a negatively regulates PTGS2 expression induced by Helicobacter pylori in human gastric epithelial cells , 2012, Journal of Gastroenterology.

[16]  J. Garcia,et al.  Differential involvement of ezrin/radixin/moesin proteins in sphingosine 1-phosphate-induced human pulmonary endothelial cell barrier enhancement. , 2011, Cellular signalling.

[17]  S. Dudek,et al.  Role of growth arrest and DNA damage-inducible α in Akt phosphorylation and ubiquitination after mechanical stress-induced vascular injury. , 2011, American journal of respiratory and critical care medicine.

[18]  Ryan M. O’Connell,et al.  NF-κB dysregulation in microRNA-146a–deficient mice drives the development of myeloid malignancies , 2011, Proceedings of the National Academy of Sciences.

[19]  Wei Zhang,et al.  Integrating microRNAs into a system biology approach to acute lung injury. , 2011, Translational research : the journal of laboratory and clinical medicine.

[20]  W. Krzyzosiak,et al.  Practical Aspects of microRNA Target Prediction , 2011, Current molecular medicine.

[21]  E. Kriegová,et al.  Involvement of microRNAs in physiological and pathological processes in the lung , 2010, Respiratory research.

[22]  Nectarios Koziris,et al.  DIANA-microT web server: elucidating microRNA functions through target prediction , 2009, Nucleic Acids Res..

[23]  Ryan M. O’Connell,et al.  Inositol phosphatase SHIP1 is a primary target of miR-155 , 2009, Proceedings of the National Academy of Sciences.

[24]  A. Mantovani,et al.  Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals , 2009, Proceedings of the National Academy of Sciences.

[25]  D. Bartel.  MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[26]  S. Ye,et al.  Critical role of PBEF expression in pulmonary cell inflammation and permeability , 2009, Cell biology international.

[27]  Bing Su,et al.  Small but influential: the role of microRNAs on gene regulatory network and 3'UTR evolution. , 2009, Journal of genetics and genomics = Yi chuan xue bao.

[28]  J. Barker,et al.  Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis , 2009, BMC Neuroscience.

[29]  B. Simon,et al.  Augmentation of Pulmonary Epithelial Cell IL-8 Expression and Permeability by Pre-B-cell Colony Enhancing Factor , 2008, Journal of Inflammation.

[30]  Y. Lussier,et al.  Essential role of pre-B-cell colony enhancing factor in ventilator-induced lung injury. , 2008, American journal of respiratory and critical care medicine.

[31]  M. Fasshauer,et al.  Visfatin/PBEF/Nampt: structure, regulation and potential function of a novel adipokine. , 2008, Clinical science.

[32]  R. Place,et al.  MicroRNA-373 induces expression of genes with complementary promoter sequences , 2008, Proceedings of the National Academy of Sciences.

[33]  Doron Betel,et al.  The microRNA.org resource: targets and expression , 2007, Nucleic Acids Res..

[34]  J. Steitz,et al.  Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation , 2007, Science.

[35]  M. Lindsay,et al.  Expression profiling in vivo demonstrates rapid changes in lung microRNA levels following lipopolysaccharide-induced inflammation but not in the anti-inflammatory action of glucocorticoids , 2007, BMC Genomics.

[36]  L. Lim,et al.  MicroRNA targeting specificity in mammals: determinants beyond seed pairing. , 2007, Molecular cell.

[37]  D. Christiani,et al.  Pre-B-cell colony-enhancing factor gene polymorphisms and risk of acute respiratory distress syndrome* , 2007, Critical care medicine.

[38]  S. Tonstad,et al.  Increased Expression of Visfatin in Macrophages of Human Unstable Carotid and Coronary Atherosclerosis: Possible Role in Inflammation and Plaque Destabilization , 2007, Circulation.

[39]  M. Matthay,et al.  Treatment of acute lung injury: historical perspective and potential future therapies. , 2006, Seminars in respiratory and critical care medicine.

[40]  Anton J. Enright,et al.  Zebrafish MiR-430 Promotes Deadenylation and Clearance of Maternal mRNAs , 2006, Science.

[41]  T. Beaty,et al.  Novel polymorphisms in the myosin light chain kinase gene confer risk for acute lung injury. , 2006, American journal of respiratory cell and molecular biology.

[42]  Ligang Wu,et al.  MicroRNAs direct rapid deadenylation of mRNA. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[43]  R. Russell,et al.  Animal MicroRNAs Confer Robustness to Gene Expression and Have a Significant Impact on 3′UTR Evolution , 2005, Cell.

[44]  S. Ye,et al.  Pre-B-cell-colony-enhancing factor is critically involved in thrombin-induced lung endothelial cell barrier dysregulation. , 2005, Microvascular research.

[45]  Diane P. Martin,et al.  Incidence and outcomes of acute lung injury. , 2005, The New England journal of medicine.

[46]  A. Pasquinelli,et al.  Regulation by let-7 and lin-4 miRNAs Results in Target mRNA Degradation , 2005, Cell.

[47]  K. Lindblad-Toh,et al.  Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals , 2005, Nature.

[48]  T. Standiford,et al.  Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury. , 2005, American journal of respiratory and critical care medicine.

[49]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[50]  A. Dembińska-kieć,et al.  Visfatin - new adipokine , 2005 .

[51]  H. Lodish,et al.  Medicine. Visfatin: a new adipokine. , 2005, Science.

[52]  J. Marshall,et al.  Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. , 2004, The Journal of clinical investigation.

[53]  D. Gigot,et al.  Pre‐B‐cell colony‐enhancing factor, whose expression is up‐regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis , 2002, European journal of immunology.

[54]  A. Verin,et al.  Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. , 2001, The Journal of clinical investigation.

[55]  S. Ognjanovic,et al.  Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes. , 2001, Journal of molecular endocrinology.