{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T13:14:42Z","timestamp":1792502082114,"version":"4.5.0"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:00:00Z","timestamp":1661472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["HL128371"],"award-info":[{"award-number":["HL128371"]}]},{"name":"Children\u2019s Wisconsin Foundation"},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["1-19-ICTS-129"],"award-info":[{"award-number":["1-19-ICTS-129"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["DK125014; DK121528"],"award-info":[{"award-number":["DK125014; DK121528"]}]},{"name":"National Institute of Health","award":["HL136597; HL144519"],"award-info":[{"award-number":["HL136597; HL144519"]}]},{"DOI":"10.13039\/100008980","name":"Medical College of Wisconsin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008980","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Children\u2019s Research Institute Pilot Innovative Research Grant"},{"name":"Department of Pediatrics Internal Support"},{"DOI":"10.13039\/100008980","name":"Medical College of Wisconsin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008980","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Children\u2019s Research Institute - Program Support"},{"name":"Research Unit Leader"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Myeloperoxidase (MPO), oxidative stress (OS), and endoplasmic reticulum (ER) stress are increased in the lungs of rat pups raised in hyperoxia, an established model of bronchopulmonary dysplasia (BPD). However, the relationship between OS, MPO, and ER stress has not been examined in hyperoxia rat pups. We treated Sprague-Dawley rat pups with tunicamycin or hyperoxia to determine this relationship. ER stress was detected using immunofluorescence, transcriptomic, proteomic, and electron microscopic analyses. Immunofluorescence observed increased ER stress in the lungs of hyperoxic rat BPD and human BPD. Proteomic and morphometric studies showed that tunicamycin directly increased ER stress of rat lungs and decreased lung complexity with a BPD phenotype. Previously, we showed that hyperoxia initiates a cycle of destruction that we hypothesized starts from increasing OS through MPO accumulation and then increases ER stress to cause BPD. To inhibit ER stress, we used tauroursodeoxycholic acid (TUDCA), a molecular chaperone. To break the cycle of destruction and reduce OS and MPO, we used N-acetyl-lysyltyrosylcysteine amide (KYC). The fact that TUDCA improved lung complexity in tunicamycin- and hyperoxia-treated rat pups supports the idea that ER stress plays a causal role in BPD. Additional support comes from data showing TUDCA decreased lung myeloid cells and MPO levels in the lungs of tunicamycin- and hyperoxia-treated rat pups. These data link OS and MPO to ER stress in the mechanisms mediating BPD. KYC\u2019s inhibition of ER stress in the tunicamycin-treated rat pup\u2019s lung provides additional support for the idea that MPO-induced ER stress plays a causal role in the BPD phenotype. ER stress appears to expand our proposed\n                    <jats:bold>\n                      <jats:italic>cycle of destruction<\/jats:italic>\n                    <\/jats:bold>\n                    . Our results suggest ER stress evolves from OS and MPO to increase neonatal lung injury and impair growth and development. The encouraging effect of TUDCA indicates that this compound has the potential for treating BPD.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0269564","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T13:46:06Z","timestamp":1661521566000},"page":"e0269564","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Role of endoplasmic reticulum stress in impaired neonatal lung growth and bronchopulmonary dysplasia"],"prefix":"10.1371","volume":"17","author":[{"given":"Kirkwood A.","family":"Pritchard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xigang","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeleye J.","family":"Afolayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9027-5686","authenticated-orcid":true,"given":"Jason","family":"Jarzembowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billy W.","family":"Day","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Naylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Hessner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Ganesh","family":"Konduri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4321-2452","authenticated-orcid":true,"given":"Ru-Jeng","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"pone.0269564.ref001","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41572-019-0127-7","article-title":"Bronchopulmonary dysplasia.","volume":"5","author":"B Th\u00e9baud","year":"2019","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"pone.0269564.ref002","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3390\/jcm6010004","article-title":"Bronchopulmonary Dysplasia: Chronic Lung Disease of Infancy and Long-Term Pulmonary Outcomes","volume":"6","author":"LM Davidson","year":"2017","journal-title":"J Clin Med"},{"key":"pone.0269564.ref003","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1164\/rccm.200507-1140OC","article-title":"Lung function and exercise capacity in young adults born prematurely.","volume":"173","author":"EJLE Vrijlandt","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"issue":"Suppl 3","key":"pone.0269564.ref004","doi-asserted-by":"crossref","first-page":"S146","DOI":"10.1513\/AnnalsATS.201312-424LD","article-title":"Bronchopulmonary dysplasia: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases","volume":"11","author":"CT McEvoy","year":"2014","journal-title":"Ann Am Thorac Soc"},{"key":"pone.0269564.ref005","doi-asserted-by":"crossref","first-page":"1179556518817322","DOI":"10.1177\/1179556518817322","article-title":"Bronchopulmonary Dysplasia: An Update of Current Pharmacologic Therapies and New Approaches.","volume":"12","author":"Z Michael","year":"2018","journal-title":"Clin Med Insights Pediatr."},{"issue":"1","key":"pone.0269564.ref006","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1542\/peds.2010-3875","article-title":"Targeting inflammation to prevent bronchopulmonary dysplasia: can new insights be translated into therapies?","volume":"128","author":"CJ Wright","year":"2011","journal-title":"Pediatrics"},{"key":"pone.0269564.ref007","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/MOP.0b013e3283423e51","article-title":"Future applications of antioxidants in premature infants.","volume":"23","author":"JW Lee","year":"2011","journal-title":"Curr Opin Pediatr"},{"issue":"4","key":"pone.0269564.ref008","doi-asserted-by":"crossref","first-page":"e189","DOI":"10.1542\/neo.20-4-e189","article-title":"Prevention of Bronchopulmonary Dysplasia: A Summary of Evidence-Based Strategies.","volume":"20","author":"EA Jensen","year":"2019","journal-title":"NeoReviews"},{"key":"pone.0269564.ref009","doi-asserted-by":"crossref","first-page":"L948","DOI":"10.1152\/ajplung.00160.2014","article-title":"Animal models of bronchopulmonary dysplasia. The term rat models","volume":"307","author":"M O\u2019Reilly","year":"2014","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"pone.0269564.ref010","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.freeradbiomed.2021.02.006","article-title":"N-acetyl-lysyltyrosylcysteine amide, a novel systems pharmacology agent, reduces bronchopulmonary dysplasia in hyperoxic neonatal rat pups","volume":"166","author":"RJ Teng","year":"2021","journal-title":"Free Radic Biol Med"},{"key":"pone.0269564.ref011","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1165\/rcmb.2012-0381OC","article-title":"Hyperoxia and interferon\u2013\u03b3\u2013induced injury in developing lungs occur via cyclooxygenase-2 and the endoplasmic reticulum stress-dependent pathway","volume":"48","author":"R Choo-Wing","year":"2013","journal-title":"Am J Respir Cell Mol Biol"},{"key":"pone.0269564.ref012","first-page":"33","article-title":"Hyperoxia induces endoplasmic reticulum stress\u2011associated apoptosis via the IRE1alpha; pathway in rats with bronchopulmonary dysplasia","volume":"23","author":"X Tong","year":"2021","journal-title":"Mol Med Rep 2021"},{"key":"pone.0269564.ref013","doi-asserted-by":"crossref","first-page":"L586","DOI":"10.1152\/ajplung.00405.2016","article-title":"Attenuation of endoplasmic reticulum stress by caffeine ameliorates hyperoxia-induced lung injury","volume":"312","author":"RJ Teng","year":"2017","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"pone.0269564.ref014","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nature07203","article-title":"From endoplasmic-reticulum stress to the inflammatory response","volume":"454","author":"K Zhang","year":"2008","journal-title":"Nature"},{"key":"pone.0269564.ref015","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0092-8674(79)90370-2","article-title":"Glycoprotein synthesis and inhibition of glycosylation by tunicamycin in preimplantation mouse embryos: compaction and trophoblast adhesion","volume":"18","author":"MA Surani","year":"1979","journal-title":"Cell"},{"key":"pone.0269564.ref016","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1053\/jhep.2002.35441","article-title":"Effect of tauroursodeoxycholic acid on endoplasmic reticulum stress-induced caspase-12 activation","volume":"36","author":"Q Xie","year":"2002","journal-title":"Hepatology"},{"key":"pone.0269564.ref017","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1681\/ASN.2007070745","article-title":"Preconditioning with endoplasmic reticulum stress ameliorates mesangioproliferative glomerulonephritis.","volume":"19","author":"R Inagi","year":"2008","journal-title":"JASN"},{"key":"pone.0269564.ref018","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human.","volume":"7","author":"AB Nair","year":"2016","journal-title":"J Basic Clin Pharm"},{"key":"pone.0269564.ref019","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1067\/mpd.2002.125802","article-title":"Tauroursodeoxycholic acid (TUDCA) in the prevention of total parenteral nutrition-associated liver disease.","volume":"141","author":"JE Heubi","year":"2002","journal-title":"J Pediatr"},{"key":"pone.0269564.ref020","doi-asserted-by":"crossref","first-page":"34702","DOI":"10.1038\/srep34702","article-title":"Chemical chaperone TUDCA prevents apoptosis and improves survival during polymicrobial sepsis in mice","volume":"6","author":"M Doerflinger","year":"2016","journal-title":"Sci Rep"},{"key":"pone.0269564.ref021","doi-asserted-by":"crossref","first-page":"6087","DOI":"10.1073\/pnas.1031632100","article-title":"Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats","volume":"100","author":"CMP Rodrigues","year":"2003","journal-title":"Proc Nat Acad Sci"},{"key":"pone.0269564.ref022","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/0024-3205(85)90080-3","article-title":"Inhibition of protein synthesis: a basis for tunicamycin-induced decrease in rat liver cytochrome P-450","volume":"37","author":"Y Singh","year":"1985","journal-title":"Life Sci"},{"key":"pone.0269564.ref023","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1164\/rccm.200809-1522ST","article-title":"An official research policy statement of the American Thoracic Society\/European Respiratory Society: Standards for quantitative assessment of lung structure","volume":"181","author":"on behalf of the ATS\/ERS Joint Task Force on the Quantitative Assessment of Lung Structure","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0269564.ref024","doi-asserted-by":"crossref","first-page":"e0190351","DOI":"10.1371\/journal.pone.0190351","article-title":"Modulation of the diet and gastrointestinal microbiota normalizes systemic inflammation and beta-cell chemokine expression associated with autoimmune diabetes susceptibility","volume":"13","author":"AM Henschel","year":"2018","journal-title":"PloS one"},{"key":"pone.0269564.ref025","doi-asserted-by":"crossref","first-page":"R80","DOI":"10.1186\/gb-2004-5-10-r80","article-title":"Bioconductor: open software development for computational biology and bioinformatics","volume":"5","author":"RC Gentleman","year":"2004","journal-title":"Genome Biol"},{"key":"pone.0269564.ref026","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/bioinformatics\/18.1.207","article-title":"Genesis: cluster analysis of microarray data","volume":"18","author":"A Sturn","year":"2002","journal-title":"Bioinformatics"},{"issue":"Web Server issue","key":"pone.0269564.ref027","doi-asserted-by":"crossref","first-page":"W96","DOI":"10.1093\/nar\/gkq418","article-title":"ToppCluster: a multiple gene list feature analyzer for comparative enrichment clustering and network-based dissection of biological systems","volume":"38","author":"V Kaimal","year":"2010","journal-title":"Nucleic Acids Res"},{"issue":"7","key":"pone.0269564.ref028","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0092-8674(01)00611-0","article-title":"XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor","volume":"107","author":"H Yoshida","year":"2001","journal-title":"Cell"},{"key":"pone.0269564.ref029","doi-asserted-by":"crossref","first-page":"167","DOI":"10.15252\/embr.201540789","article-title":"NgBR is essential for endothelial cell glycosylation and vascular development","volume":"17","author":"EJ Park","year":"2016","journal-title":"EMBO Rep"},{"key":"pone.0269564.ref030","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nrm3440","article-title":"Endoplasmic reticulum\u2013mitochondria contacts: function of the junction","volume":"13","author":"A Rowland","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"3","key":"pone.0269564.ref031","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/sj.onc.1210638","article-title":"Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis","volume":"27","author":"A Deniaud","year":"2008","journal-title":"Oncogene"},{"key":"pone.0269564.ref032","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.abb.2018.12.018","article-title":"Mitochondria-associated endoplasmic reticulum membranes in the heart","volume":"662","author":"S Wu","year":"2019","journal-title":"Arch Biochem Biophys"},{"key":"pone.0269564.ref033","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41420-019-0199-x","article-title":"DRP-1 functions independently of mitochondrial structural perturbations to facilitate BH3 mimetic-mediated apoptosis","volume":"5","author":"M Milani","year":"2019","journal-title":"Cell Death Discov"},{"key":"pone.0269564.ref034","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.molmed.2012.06.010","article-title":"ER stress-induced inflammation: does it aid or impede disease progression","volume":"18","author":"AD Garg","year":"2012","journal-title":"Trend Mol Med"},{"key":"pone.0269564.ref035","doi-asserted-by":"crossref","first-page":"3958","DOI":"10.1242\/jcs.03160","article-title":"ER stress-induced apoptosis and caspase-12 activation occurs downstream of mitochondrial apoptosis involving Apaf-1","volume":"119","author":"H Shiraishi","year":"2006","journal-title":"J Cell Sci"},{"key":"pone.0269564.ref036","first-page":"618867","volume":"9","author":"G Ferrante","year":"2021","journal-title":"Biomarkers of Oxidative Stress for Neonatal Lung Disease. Front. Pediatr"},{"key":"pone.0269564.ref037","doi-asserted-by":"crossref","first-page":"24881","DOI":"10.1074\/jbc.M004454200","article-title":"Ligand-independent dimerization activates the stress response kinases IRE1 and PERK in the lumen of the endoplasmic reticulum","volume":"275","author":"CY Liu","year":"2000","journal-title":"J Biol Chem"},{"key":"pone.0269564.ref038","doi-asserted-by":"crossref","first-page":"e1019","DOI":"10.1002\/cti2.1019","article-title":"Oxidative and endoplasmic reticulum stress in respiratory disease","volume":"7","author":"AC Chen","year":"2018","journal-title":"Clin Transl Immunology"},{"key":"pone.0269564.ref039","doi-asserted-by":"crossref","first-page":"4494","DOI":"10.3892\/mmr.2015.3979","article-title":"Activation of the endoplasmic reticulum stress pathway involving CHOP in the lungs of rats with hyperoxia\u2011induced bronchopulmonary dysplasia","volume":"12","author":"HY Lu","year":"2015","journal-title":"Mol Med Rep"},{"key":"pone.0269564.ref040","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1165\/rcmb.2015-0327OC","article-title":"The 78-kD glucose-regulated protein regulates endoplasmic reticulum homeostasis and distal epithelial cell survival during lung development","volume":"55","author":"P Flodby","year":"2016","journal-title":"Am J Respir Cell Mol Biol"},{"key":"pone.0269564.ref041","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00018-015-2052-6","article-title":"The endoplasmic reticulum: structure, function and response to cellular signaling","volume":"73","author":"DS Schwarz","year":"2016","journal-title":"Cell Mol Life Sci"},{"key":"pone.0269564.ref042","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.cell.2010.02.034","article-title":"Endoplasmic reticulum stress and the inflammatory basis of metabolic disease","volume":"140","author":"GS Hotamisligil","year":"2010","journal-title":"Cell"},{"issue":"5","key":"pone.0269564.ref043","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1165\/rcmb.2008-0341RC","article-title":"Mitochondrial dysfunction contributes to alveolar developmental arrest in hyperoxia-exposed mice","volume":"40","author":"V Ratner","year":"2009","journal-title":"Am J Respir Cell Mol Biol"},{"key":"pone.0269564.ref044","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1164\/ajrccm.164.10.2109111c","article-title":"Bronchopulmonary dysplasia: \"a vascular hypothesis\".","volume":"164","author":"SH Abman","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0269564.ref045","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41419-017-0027-2","article-title":"Mitochondria-associated membranes (MAMs) and inflammation.","volume":"9","author":"S Missiroli","year":"2018","journal-title":"Cell Death Dis"},{"issue":"4","key":"pone.0269564.ref046","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.cmet.2015.07.010","article-title":"ER Stress and Angiogenesis.","volume":"22","author":"F Binet","year":"2015","journal-title":"Cell Metab"},{"key":"pone.0269564.ref047","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1023\/A:1021664632393","article-title":"Lead-induced endoplasmic reticulum (ER) stress responses in the nervous system.","volume":"28","author":"Y Qian","year":"2003","journal-title":"Neurochem Res"},{"key":"pone.0269564.ref048","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1016\/j.febslet.2007.04.045","article-title":"ER chaperones in mammalian development and human diseases","volume":"581","author":"M Ni","year":"2007","journal-title":"FEBS Lett"},{"key":"pone.0269564.ref049","doi-asserted-by":"crossref","first-page":"5688","DOI":"10.1128\/MCB.00779-06","article-title":"GRP78\/BiP is required for cell proliferation and protecting the inner cell mass from apoptosis during early mouse embryonic development","volume":"26","author":"S Luo","year":"2006","journal-title":"Mol Cell Biol"},{"issue":"13","key":"pone.0269564.ref050","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1089\/ars.2013.5785","article-title":"Role of reactive oxygen species in neonatal pulmonary vascular disease","volume":"21","author":"S Wedgwood","year":"2014","journal-title":"Antioxid Redox Signal"},{"issue":"12 Pt 2","key":"pone.0269564.ref051","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1164\/rccm.2206007","article-title":"Reactive oxygen species and cell signaling: respiratory burst in macrophage signaling","volume":"166","author":"HJ Forman","year":"2002","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"pone.0269564.ref052","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.siny.2010.03.009","article-title":"Hyperoxia-derived lung damage in preterm infants","volume":"15","author":"V. Bhandari","year":"2010","journal-title":"Semin Fetal Neonatal Med"},{"issue":"1","key":"pone.0269564.ref053","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.2119\/molmed.2012.00314","article-title":"A Janus tale of two active high mobility group box 1 (HMGB1) redox states.","volume":"18","author":"D Tang","year":"2012","journal-title":"Mol Med"},{"issue":"1","key":"pone.0269564.ref054","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s10020-020-00172-4","article-title":"Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19?","volume":"26","author":"U Andersson","year":"2020","journal-title":"Mol Med"},{"key":"pone.0269564.ref055","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrm2199","article-title":"Signal integration in the endoplasmic reticulum unfolded protein response","volume":"8","author":"D Ron","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pone.0269564.ref056","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1089\/ars.2009.2625","article-title":"Mechanisms and implications of reactive oxygen species generation during the unfolded protein response: roles of endoplasmic reticulum oxidoreductases, mitochondrial electron transport, and NADPH oxidase","volume":"11","author":"CX Santos","year":"2009","journal-title":"Antioxid Redox Signal"},{"key":"pone.0269564.ref057","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1089\/ars.2009.2501","article-title":"Oxidative folding: cellular strategies for dealing with the resultant equimolar production of reactive oxygen species","volume":"11","author":"Y Shimizu","year":"2009","journal-title":"Antioxid Redox Signal"},{"key":"pone.0269564.ref058","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1002\/iub.1292","article-title":"Endoplasmic reticulum stress and endothelial dysfunction","volume":"66","author":"S Lenna","year":"2014","journal-title":"IUBMB Life"},{"key":"pone.0269564.ref059","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/ncb0311-184","article-title":"Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress","volume":"13","author":"I Tabas","year":"2011","journal-title":"Nat Cell Biol"},{"issue":"4","key":"pone.0269564.ref060","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1159\/000101344","article-title":"Angiogenesis in lung development, injury and repair: implications for chronic lung disease of prematurity.","volume":"91","author":"B. Th\u00e9baud","year":"2007","journal-title":"Neonatology"},{"key":"pone.0269564.ref061","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1146\/annurev-physiol-020518-114731","article-title":"Metabolic Pathways Fueling the Endothelial Cell Drive","volume":"81","author":"X Li","year":"2019","journal-title":"Annu Rev Physiol"},{"key":"pone.0269564.ref062","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3390\/cells8060544","article-title":"Glycosylation in the Tumor Microenvironment: Implications for Tumor Angiogenesis and Metastasis.","volume":"8","author":"KB Chandler","year":"2019","journal-title":"Cells"},{"key":"pone.0269564.ref063","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/978-3-319-55330-6_21","article-title":"Mitochondria and Angiogenesis","volume":"982","author":"R Marcu","year":"2017","journal-title":"Adv Exp Med Biol"},{"key":"pone.0269564.ref064","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.bbamcr.2014.02.009","article-title":"Mechanism of endoplasmic reticulum stress-induced vascular endothelial dysfunction","volume":"1843","author":"M Gal\u00e1n","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"pone.0269564.ref065","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.bbrc.2014.02.085","article-title":"Deregulated unfolded protein response in chronic wounds of diabetic ob\/ob mice: a potential connection to inflammatory and angiogenic disorders in diabetes-impaired wound healing","volume":"446","author":"C Sch\u00fcrmann","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0269564.ref066","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1016\/S0022-2275(20)34421-7","article-title":"Physicochemical properties of bile acids and their relationship to biological properties: an overview of the problem","volume":"25","author":"AE Hofmann","year":"1984","journal-title":"J Lipid Res"},{"issue":"2","key":"pone.0269564.ref067","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1542\/neo.14-2-e63","article-title":"Neonatal Cholestasis.","volume":"14","author":"AG Feldman","year":"2013","journal-title":"Neoreviews"},{"key":"pone.0269564.ref068","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1126\/science.1128294","article-title":"Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes","volume":"313","author":"U Ozcan","year":"2006","journal-title":"Science"},{"issue":"1","key":"pone.0269564.ref069","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1471-4159.2010.07092.x","article-title":"Constituents of bile, bilirubin and TUDCA, protect against oxidative stress-induced retinal degeneration","volume":"116","author":"BC Oveson","year":"2011","journal-title":"J Neurochem"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0269564","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T13:47:30Z","timestamp":1661521650000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0269564"}},"subtitle":[],"editor":[{"given":"Michael","family":"Bader","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,8,26]]},"references-count":69,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0269564","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,26]]}}}