{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:27:33Z","timestamp":1792106853160,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T00:00:00Z","timestamp":1564444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005440","name":"Center for Scientific Review","doi-asserted-by":"publisher","award":["R01 HL123766\u201001A1"],"award-info":[{"award-number":["R01 HL123766\u201001A1"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"Center for Scientific Review","doi-asserted-by":"publisher","award":["R01 HL131789"],"award-info":[{"award-number":["R01 HL131789"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and objective<\/jats:title><jats:p>Mesenchymal stem cells (MSC) have been shown to ameliorate the deleterious effects of bleomycin in murine models. However, the mechanism responsible for protection from pulmonary fibrosis by stem cell therapy is still poorly understood, especially in terms of endoplasmic reticulum (ER) stress. We hypothesized that during bleomycin\u2010induced lung injury, markers of ER stress, specifically the activation of the unfolded protein response (UPR), increase during injury, resembling the kinetics of collagen deposition in the lung described for the bleomycin model. We aimed to elucidate the possible role of MSC in ER stress modulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To determine the kinetics of ER stress in aged mice, the expression of ER stress markers after bleomycin lung injury was measured in old mice at different time points (days 0, 3, 7, 14 and 21). To evaluate the consequences of systemic delivery of MSC on lung ER stress in the bleomycin model, we evaluated changes in body weight, lung histology and protein expression of ER stress markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The level of expression of UPR transcription factor XBP\u20101 and its regulator BiP was elevated at day 7 and progressively increased up to day 21. MSC inhibited BiP expression in bleomycin\u2010induced ER stress, attenuating ER stress via the protein kinase RNA\u2010like ER kinase (PERK)\u2010Nrf2 pathway. The expression levels of other ER stress markers were not perturbed by MSC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that MSC operate on ER stress via several pathways, but the PERK\u2010Nrf2 pathway revealed to be the main functioning pathway in our bleomycin model.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.13646","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T01:34:53Z","timestamp":1564536893000},"page":"417-426","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Mesenchymal stem cells reduce ER stress via PERK\u2010Nrf2 pathway in an aged mouse model"],"prefix":"10.1111","volume":"25","author":[{"given":"Eun Joo","family":"Lee","sequence":"first","affiliation":[{"name":"The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease University of Pittsburgh  Pittsburgh PA USA"},{"name":"Division of Respiratory, Allergy and Critical Care Medicine University of Pittsburgh  Pittsburgh PA USA"},{"name":"Division of Respiratory, Allergy and Critical Care Medicine Korea University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayra","family":"C\u00e1rdenes","sequence":"additional","affiliation":[{"name":"The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease University of Pittsburgh  Pittsburgh PA USA"},{"name":"Division of Respiratory, Allergy and Critical Care Medicine University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease University of Pittsburgh  Pittsburgh PA USA"},{"name":"Division of Respiratory, Allergy and Critical Care Medicine University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6047-1670","authenticated-orcid":false,"given":"Jacobo","family":"Sellar\u00e9s","sequence":"additional","affiliation":[{"name":"The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease University of Pittsburgh  Pittsburgh PA USA"},{"name":"Division of Respiratory, Allergy and Critical Care Medicine University of Pittsburgh  Pittsburgh PA USA"},{"name":"Interstitial Lung Disease Program, Servei de Pneumologia Hospital Cl\u00ednic  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sembrat","sequence":"additional","affiliation":[{"name":"The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease University of Pittsburgh  Pittsburgh PA USA"},{"name":"Division of Respiratory, Allergy and Critical Care Medicine University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Aranda","sequence":"additional","affiliation":[{"name":"The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease University of Pittsburgh  Pittsburgh PA USA"},{"name":"Division of Respiratory, Allergy and Critical Care Medicine University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Peng","sequence":"additional","affiliation":[{"name":"The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease University of Pittsburgh  Pittsburgh PA USA"},{"name":"Division of Respiratory, Allergy and Critical Care Medicine University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Bullock","sequence":"additional","affiliation":[{"name":"The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease University of Pittsburgh  Pittsburgh PA USA"},{"name":"Division of Respiratory, Allergy and Critical Care Medicine University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed M.","family":"Nouraie","sequence":"additional","affiliation":[{"name":"The Dorothy P. and Richard P. 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