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However, the molecular mechanisms of carbon monoxide-releasing molecule (CORM)-2-induced HO-1 expression in human tracheal smooth muscle cells (HTSMCs) remain unknown. Here, we found that pretreatment with CORM-2 attenuated the lipopolysaccharide (LPS)-induced intercellular adhesion molecule (ICAM-1) expression and leukocyte count through the up-regulation of HO-1 in mice, which was revealed by immunohistochemistrical staining, Western blot, real-time PCR, and cell count. The inhibitory effects of HO-1 by CORM-2 were reversed by transfection with HO-1 siRNA. Next, Western blot, real-time PCR, and promoter activity assay were performed to examine the HO-1 induction in HTSMCs. We found that CORM-2 induced HO-1 expression via the activation of protein kinase C (PKC)\u03b1 and proline-rich tyrosine kinase (Pyk2), which was mediated through Nox-derived ROS generation using pharmacological inhibitors or small interfering ribonucleic acids (siRNAs). CORM-2-induced HO-1 expression was mediated through Nox-(1, 2, 4) or p47phox, which was confirmed by transfection with their own siRNAs. The Nox-derived ROS signals promoted the activities of extracellular signal-regulated kinase 1\/2 (ERK1\/2). Subsequently, c-Fos and c-Jun\u2014activator protein-1 (AP-1) subunits\u2014were up-regulated by activated ERK1\/2, which turned on transcription of the HO-1 gene by regulating the HO-1 promoter. These results suggested that in HTSMCs, CORM-2 activates PKC\u03b1\/Pyk2-dependent Nox\/ROS\/ERK1\/2\/AP-1, leading to HO-1 up-regulation, which suppresses the lipopolysaccharide (LPS)-induced airway inflammation.<\/jats:p>","DOI":"10.3390\/ijms20133157","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T11:20:26Z","timestamp":1561720826000},"page":"3157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Carbon Monoxide Releasing Molecule-2-Upregulated ROS-Dependent Heme Oxygenase-1 Axis Suppresses Lipopolysaccharide-Induced Airway Inflammation"],"prefix":"10.3390","volume":"20","author":[{"given":"Chih-Chung","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Anesthetics, Chang Gung Memorial Hospital at Linkuo, and College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 33302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Der","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Anesthetics, Chang Gung Memorial Hospital at Linkuo, and College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 33302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8970-5562","authenticated-orcid":false,"given":"Rou-Ling","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, 259 Wen-Hwa 1 Road, Kwei-San, Tao-Yuan 33302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuen-Mao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthetics, Chang Gung Memorial Hospital at Linkuo, and College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 33302, Taiwan"},{"name":"Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, 259 Wen-Hwa 1 Road, Kwei-San, Tao-Yuan 33302, Taiwan"},{"name":"Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Tao-Yuan 33302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1146\/annurev.pharmtox.37.1.517","article-title":"The heme oxygenase system: A regulator of second messenger gases","volume":"37","author":"Maines","year":"1997","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1152\/physrev.00011.2005","article-title":"Heme oxygenase-1\/carbon monoxide: From basic science to therapeutic applications","volume":"86","author":"Ryter","year":"2006","journal-title":"Physiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1073\/pnas.61.2.748","article-title":"The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase","volume":"61","author":"Tenhunen","year":"1968","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S1471-4906(03)00181-9","article-title":"Heme oxygenase-1: Unleashing the protective properties of heme","volume":"24","author":"Otterbein","year":"2003","journal-title":"Trends Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5098","DOI":"10.4049\/jimmunol.181.7.5098","article-title":"Lipoteichoic acid induces HO-1 expression via the TLR2\/MyD88\/c-Src\/NADPH oxidase pathway and Nrf2 in human tracheal smooth muscle cells","volume":"181","author":"Lee","year":"2008","journal-title":"J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18148","DOI":"10.1016\/S0021-9258(19)37165-0","article-title":"Ferritin: A cytoprotective antioxidant strategem of endothelium","volume":"267","author":"Balla","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11010-006-9190-y","article-title":"Carbon monoxide and bilirubin from heme oxygenase-1 suppresses reactive oxygen species generation and plasminogen activator inhibitor-1 induction","volume":"291","author":"Matsumoto","year":"2006","journal-title":"Mol. Cell. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/cmi.2015.02","article-title":"IRG1 induced by heme oxygenase-1\/carbon monoxide inhibits LPS-mediated sepsis and pro-inflammatory cytokine production","volume":"13","author":"Joe","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8008","DOI":"10.1038\/sj.bjp.0706241","article-title":"Carbon monoxide-releasing molecules (CO-RMs) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages","volume":"145","author":"Sawle","year":"2005","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4408","DOI":"10.4049\/jimmunol.175.7.4408","article-title":"Lipopolysaccharide-induced heme oxygenase-1 expression in human monocytic cells is mediated via Nrf2 and protein kinase C","volume":"175","author":"Rushworth","year":"2005","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/j.cellsig.2006.02.001","article-title":"Involvement of JNKs and p38-MAPK\/MSK1 pathways in H2O2-induced upregulation of heme oxygenase-1 mRNA in H9c2 cells","volume":"18","author":"Aggeli","year":"2006","journal-title":"Cell Signal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1165\/rcmb.2006-0331TR","article-title":"The role of heme oxygenase-1 in pulmonary disease","volume":"36","author":"Fredenburgh","year":"2007","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"473","DOI":"10.2174\/138161208783597399","article-title":"Inducers of heme oxygenase-1","volume":"14","author":"Ferrandiz","year":"2008","journal-title":"Curr. Pharm. Des."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"519","DOI":"10.2353\/ajpath.2009.090016","article-title":"Overexpression of HO-1 protects against TNF-alpha-mediated airway inflammation by down-regulation of TNFR1-dependent oxidative stress","volume":"175","author":"Lee","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.bcp.2012.05.005","article-title":"Role of NADPH oxidase\/ROS in pro-inflammatory mediators-induced airway and pulmonary diseases","volume":"84","author":"Lee","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.molimm.2013.04.002","article-title":"Molecular mechanisms of reactive oxygen species-related pulmonary inflammation and asthma","volume":"56","author":"Zuo","year":"2013","journal-title":"Mol. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1172\/JCI5342","article-title":"Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury","volume":"103","author":"Otterbein","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, F.J., Duggal, R.N., Oliva, O.M., Karki, S., Surolia, R., Wang, Z., Watson, R.D., Thannickal, V.J., Powell, M., and Watts, S. (2015). Heme oxygenase-1 protects corexit 9500A-induced respiratory epithelial injury across species. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122275"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.bcp.2005.10.042","article-title":"CO from enhanced HO activity or from CORM-2 inhibits both O2- and NO production and downregulates HO-1 expression in LPS-stimulated macrophages","volume":"71","author":"Srisook","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1016\/j.freeradbiomed.2010.02.026","article-title":"Cigarette smoke particle-phase extract induces HO-1 expression in human tracheal smooth muscle cells: Role of the c-Src\/NADPH oxidase\/MAPK\/Nrf2 signaling pathway","volume":"48","author":"Cheng","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"794237","DOI":"10.1155\/2012\/794237","article-title":"Regulation of ROS production and vascular function by carbon monoxide","volume":"2012","author":"Choi","year":"2012","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s12035-014-8869-4","article-title":"CO Induces Nrf2-Dependent Heme Oxygenase-1 Transcription by Cooperating with Sp1 and c-Jun in Rat Brain Astrocytes","volume":"52","author":"Chi","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25350","DOI":"10.1074\/jbc.M503512200","article-title":"Mitochondrial respiratory chain and NAD(P)H oxidase are targets for the antiproliferative effect of carbon monoxide in human airway smooth muscle","volume":"280","author":"Taille","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1089\/15230860260220111","article-title":"Regulation of heme oxygenase-1 by redox signals involving nitric oxide","volume":"4","author":"Motterlini","year":"2002","journal-title":"Antioxid. Redox Signal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"791231","DOI":"10.1155\/2013\/791231","article-title":"Inflammatory signalings involved in airway and pulmonary diseases","volume":"2013","author":"Lee","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/nrd3228","article-title":"The therapeutic potential of carbon monoxide","volume":"9","author":"Motterlini","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1002\/jcp.24912","article-title":"c-Src-dependent transactivation of EGFR mediates CORM-2-induced HO-1 expression in human tracheal smooth muscle cells","volume":"230","author":"Yang","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1165\/rcmb.2006-0340TR","article-title":"How many transcription factors does it take to turn on the heme oxygenase-1 gene?","volume":"36","author":"Alam","year":"2007","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"26071","DOI":"10.1074\/jbc.274.37.26071","article-title":"Nrf2, a Cap\u2019n\u2019Collar transcription factor, regulates induction of the heme oxygenase-1 gene","volume":"274","author":"Alam","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"859235","DOI":"10.1155\/2012\/859235","article-title":"Therapeutic potential of heme oxygenase-1\/carbon monoxide in lung disease","volume":"2012","author":"Constantin","year":"2012","journal-title":"Int. J. Hypertens."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1172\/JCI71362","article-title":"Carbon monoxide-based therapy ameliorates acute pancreatitis via TLR4 inhibition","volume":"124","author":"Xue","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Qin, W., Zhang, J., Lv, W., Wang, X., and Sun, B. (2013). Effect of carbon monoxide-releasing molecules II-liberated CO on suppressing inflammatory response in sepsis by interfering with nuclear factor kappa B activation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075840"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1124\/jpet.110.175216","article-title":"Carbon monoxide involved in modulating HCO3\u2212 secretion in rat duodenum","volume":"337","author":"Takasuka","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1042\/BJ20130220","article-title":"Protein kinase C pharmacology: Refining the toolbox","volume":"452","author":"Newton","year":"2013","journal-title":"Biochem. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5833","DOI":"10.1007\/s12035-015-9485-7","article-title":"Thrombin\/Matrix Metalloproteinase-9-Dependent SK-N-SH Cell Migration is Mediated Through a PLC\/PKC\/MAPKs\/NF-kappaB Cascade","volume":"53","author":"Yang","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8677","DOI":"10.1074\/jbc.M114.633107","article-title":"A role for the tyrosine kinase Pyk2 in depolarization-induced contraction of vascular smooth muscle","volume":"290","author":"Mills","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1128\/MCB.00197-13","article-title":"Macrophage fusion is controlled by the cytoplasmic protein tyrosine phosphatase PTP-PEST\/PTPN12","volume":"33","author":"Rhee","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1089\/ars.2009.2957","article-title":"Reactive Oxygen Species-Dependent c-Fos\/Activator Protein 1 Induction Upregulates Heme Oxygenase-1 Expression by Bradykinin in Brain Astrocytes","volume":"13","author":"Hsieh","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.pharmthera.2012.09.007","article-title":"Carbon monoxide: Mechanisms of action and potential clinical implications","volume":"137","author":"Rochette","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0898-6568(98)00037-0","article-title":"Redox regulation of cellular signalling","volume":"11","author":"Kamata","year":"1999","journal-title":"Cell Signal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1183\/09031936.98.11020384","article-title":"Hydrogen peroxide-induced epithelial injury: The protective role of intracellular nonprotein thiols (NPSH)","volume":"11","author":"Mulier","year":"1998","journal-title":"Eur. Respir. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.freeradbiomed.2004.04.020","article-title":"Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH oxidase and glutathione redox-dependent mechanisms","volume":"37","author":"Barbieri","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_43","first-page":"1395","article-title":"Rho GTPases and Nox dependent ROS production in skin. Is there a connection?","volume":"27","author":"Stanley","year":"2012","journal-title":"Histol. Histopathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"26708","DOI":"10.1074\/jbc.M111.255752","article-title":"Reactive oxygen species mediate bactericidal killing elicited by carbon monoxide-releasing molecules","volume":"286","author":"Tavares","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0034-5687(99)00019-5","article-title":"NO and CO as second messengers in oxygen sensing in the carotid body","volume":"115","author":"Prabhakar","year":"1999","journal-title":"Respir. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1038\/nm.4188","article-title":"Dual effects of carbon monoxide on pericytes and neurogenesis in traumatic brain injury","volume":"22","author":"Choi","year":"2016","journal-title":"Nat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1365-2222.2010.03658.x","article-title":"Mitogen-activated protein kinase signalling and ERK1\/2 bistability in asthma","volume":"41","author":"Alam","year":"2011","journal-title":"Clin. Exp. Allergy"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1002\/mc.20234","article-title":"Butylated hydroxyanisole regulates ARE-mediated gene expression via Nrf2 coupled with ERK and JNK signaling pathway in HepG2 cells","volume":"45","author":"Yuan","year":"2006","journal-title":"Mol. Carcinog."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s00134-008-1011-1","article-title":"Use of carbon monoxide as a therapeutic agent: Promises and challenges","volume":"34","author":"Foresti","year":"2008","journal-title":"Intensive Care Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/jnr.20180","article-title":"Redox regulation of glial inflammatory response to lipopolysaccharide and interferongamma","volume":"77","author":"Pawate","year":"2004","journal-title":"J. Neurosci. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/j.freeradbiomed.2005.11.024","article-title":"Heme oxygenase-1 contributes to the cytoprotection of alpha-lipoic acid via activation of p44\/42 mitogen-activated protein kinase in vascular smooth muscle cells","volume":"40","author":"Cheng","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1096\/fasebj.10.7.8635688","article-title":"Antioxidant and redox regulation of gene transcription","volume":"10","author":"Sen","year":"1996","journal-title":"FASEB J."},{"key":"ref_53","first-page":"924","article-title":"Regulation of heme oxygenase-1 gene transcription: Recent advances and highlights from the International Conference (Uppsala, 2003) on Heme Oxygenase","volume":"6","author":"Alam","year":"2004","journal-title":"Antioxid. Redox Signal."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1124\/jpet.106.117218","article-title":"Carbon monoxide-releasing molecules modulate leukocyte-endothelial interactions under flow","volume":"321","author":"Urquhart","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"L26","DOI":"10.1152\/ajplung.00237.2003","article-title":"Heme oxygenase attenuates allergen-induced airway inflammation and hyperreactivity in guinea pigs","volume":"287","author":"Almolki","year":"2004","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jss.2006.08.032","article-title":"Role of CO-releasing molecules liberated CO in attenuating leukocytes sequestration and inflammatory responses in the lung of thermally injured mice","volume":"139","author":"Sun","year":"2007","journal-title":"J. Surg. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1111\/j.1476-5381.2010.00872.x","article-title":"Animal research: Reporting in vivo experiments: The ARRIVE guidelines","volume":"160","author":"Kilkenny","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"260530","DOI":"10.1155\/2015\/260530","article-title":"Inhibitory Effect of a French Maritime Pine Bark Extract-Based Nutritional Supplement on TNF-alpha-Induced Inflammation and Oxidative Stress in Human Coronary Artery Endothelial Cells","volume":"2015","author":"McGrath","year":"2015","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"L521","DOI":"10.1152\/ajplung.00274.2013","article-title":"Nox2\/ROS-dependent human antigen R translocation contributes to TNF-alpha-induced SOCS-3 expression in human tracheal smooth muscle cells","volume":"306","author":"Hsu","year":"2014","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"L921","DOI":"10.1152\/ajplung.00124.2003","article-title":"Lipoteichoic acid-stimulated p42\/p44 MAPK activation via Toll-like receptor 2 in tracheal smooth muscle cells","volume":"286","author":"Lee","year":"2004","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s12035-013-8442-6","article-title":"High glucose induces reactive oxygen species-dependent matrix metalloproteinase-9 expression and cell migration in brain astrocytes","volume":"48","author":"Hsieh","year":"2013","journal-title":"Mol. 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