MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome

BMC Medical Genomics

Lin Liu¹  Yang Wang³  Melanie Breshears²  Narendranath Reddy Chintagari³  Xiao Xiao³  Chaoqun Huang² 

[1] Department of Physiological Sciences, Oklahoma State University, 264 McElroy Hall, Stillwater, OK 74078, USA;Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, USA;Department of Physiological Sciences, Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Stillwater, OK, USA

关键词: ARDS;    Microarray;    mRNA;    MicroRNA;   

Others  :  1090737
DOI  :  10.1186/1755-8794-7-46

 received in 2013-10-07, accepted in 2014-07-16,  发布年份 2014

【 摘 要 】

Background

Acute respiratory distress syndrome (ARDS) is characterized by pulmonary epithelial injury and extensive inflammation of the pulmonary parenchyma. Systematic analyses of microRNA (miRNA) and mRNA expression profiling in ARDS provide insights into understanding of molecular mechanisms of the pathogenesis of ARDS. The objective of this study was to identify miRNA and mRNA interactions in a rat model of ARDS by combining miRNA and mRNA microarray analyses.

Methods

Rat model of ARDS was induced by saline lavage and mechanical ventilation. The expression profiles of both mRNAs and miRNAs in rat ARDS model were performed by microarray analyses. Microarray data were further verified by quantitative RT-PCR. Functional annotation on dys-regulated mRNAs and miRNAs was carried out by bioinformatics analysis.

Results

The expression of 27 miRNAs and 37 mRNAs were found to be significantly changed. The selected miRNAs and genes were further verified by quantitative real-time PCR. The down-regulated miRNAs included miR-24, miR-26a, miR-126, and Let-7a, b, c, f. The up-regulated miRNAs were composed of miR-344, miR-346, miR-99a, miR-127, miR-128b, miR-135b, and miR-30a/b. Gene ontology and functional annotation analyses indicated that up-regulated mRNAs, such as Apc, Timp1, and Sod2, were involved in the regulation of apoptosis. Bioinformatics analysis showed the inverse correlation of altered miRNAs with the expression of their predicted target mRNAs. While Sod2 was inversely correlated with Let-7a, b, c, f., Ebf1 and Apc were inversely correlated with miR-24 and miR-26a, respectively. miR-26a, miR-346, miR-135b, miR-30a/b, miR-344, and miR-18a targeted multiple altered mRNAs. Gabrb1, Sod2, Eif2ak1, Fbln5, and Tspan8 were targeted by multiple altered miRNAs.

Conclusion

The expressions of miRNAs and mRNAs were altered in a rat model of ARDS. The identified miRNA-mRNA pairs may play critical roles in the pathogenesis of ARDS.

【 授权许可】

   
2014 Huang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】

• [1]Malhotra A: Low-tidal-volume ventilation in the acute respiratory distress syndrome. N Engl J Med 2007, 357(11):1113-1120.
• [2]Mikkelsen ME, Shah CV, Meyer NJ, Gaieski DF, Lyon S, Miltiades AN, Goyal M, Fuchs BD, Bellamy SL, Christie JD: The epidemiology of acute respiratory distress syndrome in patients presenting to the emergency department with severe sepsis. Shock 2013, 40(5):375-381.
• [3]Holland MC, Mackersie RC, Morabito D, Campbell AR, Kivett VA, Patel R, Erickson VR, Pittet JF: The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury. J Trauma 2003, 55(1):106-111.
• [4]Ferring M, Vincent JL: Is outcome from ARDS related to the severity of respiratory failure? Eur Respir J 1997, 10(6):1297-1300.
• [5]Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD: Incidence and outcomes of acute lung injury. N Engl J Med 2005, 353(16):1685-1693.
• [6]Grommes J, Soehnlein O: Contribution of neutrophils to acute lung injury. Mol Med 2011, 17(3–4):293-307.
• [7]Matthay MA, Zemans RL: The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol 2011, 6:147-163.
• [8]Lowe K, Alvarez D, King J, Stevens T: Phenotypic heterogeneity in lung capillary and extra-alveolar endothelial cells. Increased extra-alveolar endothelial permeability is sufficient to decrease compliance. J Surg Res 2007, 143(1):70-77.
• [9]Wang Y, Brahmakshatriya V, Zhu H, Lupiani B, Reddy SM, Yoon BJ, Gunaratne PH, Kim JH, Chen R, Wang J, Zhou H: Identification of differentially expressed miRNAs in chicken lung and trachea with avian influenza virus infection by a deep sequencing approach. BMC Genomics 2009, 10:512.
• [10]Lu Y, Okubo T, Rawlins E, Hogan BL: Epithelial progenitor cells of the embryonic lung and the role of microRNAs in their proliferation. Proc Am Thorac Soc 2008, 5(3):300-304.
• [11]Carraro G, El-Hashash A, Guidolin D, Tiozzo C, Turcatel G, Young BM, De Langhe SP, Bellusci S, Shi W, Parnigotto PP, Warburton D: miR-17 family of microRNAs controls FGF10-mediated embryonic lung epithelial branching morphogenesis through MAPK14 and STAT3 regulation of E-Cadherin distribution. Dev Biol 2009, 333(2):238-250.
• [12]Bhaskaran M, Wang Y, Zhang H, Weng T, Baviskar P, Guo Y, Gou D, Liu L: MicroRNA-127 modulates fetal lung development. Physiol Genomics 2009, 37(3):268-278.
• [13]Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY, Srivastava D: miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 2008, 15(2):272-284.
• [14]Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, Richardson JA, Bassel-Duby R, Olson EN: The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell 2008, 15(2):261-271.
• [15]Vaporidi K, Vergadi E, Kaniaris E, Hatziapostolou M, Lagoudaki E, Georgopoulos D, Zapol WM, Bloch KD, Iliopoulos D: Pulmonary microRNA profiling in a mouse model of ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 2012, 303(3):L199-L207.
• [16]Zhang X, Peng W, Zhang S, Wang C, He X, Zhang Z, Zhu L, Wang Y, Feng Z: MicroRNA expression profile in hyperoxia-exposed newborn mice during the development of bronchopulmonary dysplasia. Respir Care 2011, 56(7):1009-1015.
• [17]Bhaskaran M, Xi D, Wang Y, Huang C, Narasaraju T, Shu W, Zhao C, Xiao X, More S, Breshears M, Liu L: Identification of microRNAs changed in the neonatal lungs in response to hyperoxia exposure. Physiol Genomics 2012, 44(20):970-980.
• [18]Ezzie ME, Crawford M, Cho JH, Orellana R, Zhang S, Gelinas R, Batte K, Yu L, Nuovo G, Galas D, Diaz P, Wang K, Nana-Sinkam SP: Gene expression networks in COPD: microRNA and mRNA regulation. Thorax 2012, 67(2):122-131.
• [19]Pottelberge GR, Mestdagh P, Bracke KR, Thas O, Durme YM, Joos GF, Vandesompele J, Brusselle GG: MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2011, 183(7):898-906.
• [20]Pandit KV, Corcoran D, Yousef H, Yarlagadda M, Tzouvelekis A, Gibson KF, Konishi K, Yousem SA, Singh M, Handley D, Richards T, Selman M, Watkins SC, Pardo A, Ben-Yehudah A, Bouros D, Eickelberg O, Ray P, Benos PV, Kaminski N: Inhibition and role of let-7d in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2010, 182(2):220-229.
• [21]Liu G, Friggeri A, Yang Y, Milosevic J, Ding Q, Thannickal VJ, Kaminski N, Abraham E: miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med 2010, 207(8):1589-1597.
• [22]Ware LB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med 2000, 342(18):1334-1349.
• [23]Meyer NJ, Garcia JG: Wading into the genomic pool to unravel acute lung injury genetics. Proc Am Thorac Soc 2007, 4(1):69-76.
• [24]Zhou T, Garcia JG, Zhang W: Integrating microRNAs into a system biology approach to acute lung injury. Transl Res 2011, 157(4):180-190.
• [25]Germann PG, Hafner D: A rat model of acute respiratory distress syndrome (ARDS): Part 1. Time dependency of histological and pathological changes. J Pharmacol Toxicol Methods 1998, 40(2):101-107.
• [26]Yen CC, Lai YW, Chen HL, Lai CW, Lin CY, Chen W, Kuan YP, Hsu WH, Chen CM: Aerosolized human extracellular superoxide dismutase prevents hyperoxia-induced lung injury. PLoS One 2011, 6(10):e26870.
• [27]Kim KH, Burkhart K, Chen P, Frevert CW, Randolph-Habecker J, Hackman RC, Soloway PD, Madtes DK: Tissue inhibitor of metalloproteinase-1 deficiency amplifies acute lung injury in bleomycin-exposed mice. Am J Respir Cell Mol Biol 2005, 33(3):271-279.
• [28]Yue W, Dacic S, Sun Q, Landreneau R, Guo M, Zhou W, Siegfried JM, Yu J, Zhang L: Frequent inactivation of RAMP2, EFEMP1 and Dutt1 in lung cancer by promoter hypermethylation. Clin Cancer Res 2007, 13(15 Pt 1):4336-4344.
• [29]Nazarenko I, Rana S, Baumann A, McAlear J, Hellwig A, Trendelenburg M, Lochnit G, Preissner KT, Zoller M: Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res 2010, 70(4):1668-1678.
• [30]da Huang W, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009, 4(1):44-57.
• [31]da Huang W, Sherman BT, Tan Q, Kir J, Liu D, Bryant D, Guo Y, Stephens R, Baseler MW, Lane HC, Lempicki RA: DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res 2007, 35:W169-W175.
• [32]Papadopoulos GL, Alexiou P, Maragkakis M, Reczko M, Hatzigeorgiou AG: DIANA-mirPath: Integrating human and mouse microRNAs in pathways. Bioinformatics 2009, 25(15):1991-1993.
• [33]Downey GP, Dong Q, Kruger J, Dedhar S, Cherapanov V: Regulation of neutrophil activation in acute lung injury. Chest 1999, 116(1 Suppl):46S-54S.
• [34]Martin TR: Cytokines and the acute respiratory distress syndrome (ARDS): a question of balance. Nat Med 1997, 3(3):272-273.
• [35]Wada T, Jesmin S, Gando S, Yanagida Y, Mizugaki A, Sultana SN, Zaedi S, Yokota H: The role of angiogenic factors and their soluble receptors in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with critical illness. J Inflamm (Lond) 2013, 10(1):6.
• [36]Medford AR, Godinho SI, Keen LJ, Bidwell JL, Millar AB: Relationship between vascular endothelial growth factor + 936 genotype and plasma/epithelial lining fluid vascular endothelial growth factor protein levels in patients with and at risk for ARDS. Chest 2009, 136(2):457-464.
• [37]Laurent T, Markert M, Feihl F, Schaller MD, Perret C: Oxidant-antioxidant balance in granulocytes during ARDS. Effect of N-acetylcysteine. Chest 1996, 109(1):163-166.
• [38]Suarez Y, Sessa WC: MicroRNAs as novel regulators of angiogenesis. Circ Res 2009, 104(4):442-454.
• [39]Chi SW, Zang JB, Mele A, Darnell RB: Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 2009, 460(7254):479-486.
• [40]Bardales RH, Xie SS, Schaefer RF, Hsu SM: Apoptosis is a major pathway responsible for the resolution of type II pneumocytes in acute lung injury. Am J Pathol 1996, 149(3):845-852.
• [41]Lee KS, Choi YH, Kim YS, Baik SH, Oh YJ, Sheen SS, Park JH, Hwang SC, Park KJ: Evaluation of bronchoalveolar lavage fluid from ARDS patients with regard to apoptosis. Respir Med 2008, 102(3):464-469.
• [42]Suh JH, Choi E, Cha MJ, Song BW, Ham O, Lee SY, Yoon C, Lee CY, Park JH, Lee SH, Hwang KC: Up-regulation of miR-26a promotes apoptosis of hypoxic rat neonatal cardiomyocytes by repressing GSK-3beta protein expression. Biochem Biophys Res Commun 2012, 423(2):404-410.
• [43]Zhang B, Liu XX, He JR, Zhou CX, Guo M, He M, Li MF, Chen GQ, Zhao Q: Pathologically decreased miR-26a antagonizes apoptosis and facilitates carcinogenesis by targeting MTDH and EZH2 in breast cancer. Carcinogenesis 2011, 32(1):2-9.
• [44]Barh D, Malhotra R, Ravi B, Sindhurani P: MicroRNA let-7: an emerging next-generation cancer therapeutic. Curr Oncol 2010, 17(1):70-80.
• [45]Oglesby IK, Bray IM, Chotirmall SH, Stallings RL, O'Neill SJ, McElvaney NG, Greene CM: miR-126 is downregulated in cystic fibrosis airway epithelial cells and regulates TOM1 expression. J Immunol 2010, 184(4):1702-1709.
• [46]Franchina T, Amodeo V, Bronte G, Savio G, Ricciardi GR, Picciotto M, Russo A, Giordano A, Adamo V: Circulating miR-22, miR-24 and miR-34a as novel predictive biomarkers to pemetrexed-based chemotherapy in advanced non small cell lung cancer. J Cell Physiol 2013, 229(1):97-99.
• [47]Oneyama C, Ikeda J, Okuzaki D, Suzuki K, Kanou T, Shintani Y, Morii E, Okumura M, Aozasa K, Okada M: MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways. Oncogene 2011, 30(32):3489-3501.
• [48]Hayes DN, McLeod HL: EGFR regulation by microRNA in lung cancer: a rose by any other name … is an increasingly complicated rose. Ann Oncol 2008, 19(6):1036-1037.
• [49]Lin CW, Chang YL, Chang YC, Lin JC, Chen CC, Pan SH, Wu CT, Chen HY, Yang SC, Hong TM, Yang PC: MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1. Nat Comm 2013, 4:1877.
• [50]Kumarswamy R, Mudduluru G, Ceppi P, Muppala S, Kozlowski M, Niklinski J, Papotti M, Allgayer H: MicroRNA-30a inhibits epithelial-to-mesenchymal transition by targeting Snai1 and is downregulated in non-small cell lung cancer. Int J Cancer 2012, 130(9):2044-2053.
• [51]Kumar M, Ahmad T, Sharma A, Mabalirajan U, Kulshreshtha A, Agrawal A, Ghosh B: Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immunol 2011, 128(5):1077-1085. e1071-1010
• [52]Poissonnier L, Villain G, Soncin F, Mattot V: miR126-5p repression of ALCAM and SetD5 in endothelial cells regulates leucocyte adhesion and transmigration. Cardiovasc Res 2014, 102(3):436-447.
• [53]Lang JD, McArdle PJ, O'Reilly PJ, Matalon S: Oxidant-antioxidant balance in acute lung injury. Chest 2002, 122(6 Suppl):314S-320S.
• [54]Trujillo G, Zhang J, Habiel DM, Ge L, Ramadass M, Ghebrehiwet B, Kew RR: Cofactor regulation of C5a chemotactic activity in physiological fluids. Requirement for the vitamin D binding protein, thrombospondin-1 and its receptors. Mol Immunol 2011, 49(3):495-503.
• [55]Sabharwal AK, Bajaj SP, Ameri A, Tricomi SM, Hyers TM, Dahms TE, Taylor FB Jr, Bajaj MS: Tissue factor pathway inhibitor and von Willebrand factor antigen levels in adult respiratory distress syndrome and in a primate model of sepsis. Am J Respir Crit Care Med 1995, 151(3 Pt 1):758-767.
• [56]Moss M, Ackerson L, Gillespie MK, Moore FA, Moore EE, Parsons PE: von Willebrand factor antigen levels are not predictive for the adult respiratory distress syndrome. Am J Respir Crit Care Med 1995, 151(1):15-20.
• [57]Moss M, Standiford TJ: Leptin in fibroproliferative acute respiratory distress syndrome: not just a satiety factor. Am J Respir Crit Care Med 2011, 183(11):1443-1444.
• [58]Villar J, Cabrera NE, Casula M, Valladares F, Flores C, Lopez-Aguilar J, Blanch L, Zhang H, Kacmarek RM, Slutsky AS: WNT/beta-catenin signaling is modulated by mechanical ventilation in an experimental model of acute lung injury. Intensive Care Med 2011, 37(7):1201-1209.
• [59]Hafner D, Germann PG: A rat model of acute respiratory distress syndrome (ARDS) Part 2, influence of lavage volume, lavage repetition, and therapeutic treatment with rSP-C surfactant. J Pharmacol Toxicol Methods 1999, 41(2–3):97-106.
• [60]Wang Y, Weng T, Gou D, Chen Z, Chintagari NR, Liu L: Identification of rat lung-specific microRNAs by micoRNA microarray: valuable discoveries for the facilitation of lung research. BMC Genomics 2007, 8:29.
• [61]Chen Z, Liu L: RealSpot: software validating results from DNA microarray data analysis with spot images. Physiol Genomics 2005, 21(2):284-291.
• [62]Tusher VG, Tibshirani R, Chu G: Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A 2001, 98(9):5116-5121.
• [63]Chen Z, Chen J, Weng T, Jin N, Liu L: Identification of rat lung–prominent genes by a parallel DNA microarray hybridization. BMC Genomics 2006, 7:47.
• [64]Shi R, Chiang VL: Facile means for quantifying microRNA expression by real-time PCR. Biotechniques 2005, 39(4):519-525.