{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:47:58Z","timestamp":1791157678545,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Chronic obstructive pulmonary disease is frequently complicated with comorbidities, such as cardiovascular disease, osteoporosis, and body weight loss, but the causal link remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the role of adiponectin in the pathogenesis of chronic obstructive pulmonary disease and its potential use in therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adiponectin localization and dynamics in the lung were analyzed in an elastase-induced emphysema model. Next, the lung of adiponectin-knockout mice, extrapulmonary effects, and the underlying mechanism were investigated. Finally, we tested whether exogenous adiponectin could ameliorate the emphysematous change in adiponectin-knockout mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Adiponectin expression in lung vasculature and plasma concentration of adiponectin were reduced after elastase-instillation. Notably, adiponectin-knockout mice showed progressive alveolar enlargement and increased lung compliance. They further exhibited not only systemic inflammation, but also extrapulmonary phenotype, such as body weight loss, fat atrophy, and osteoporosis. Moreover, endothelial apoptosis was enhanced in the lungs of adiponectin-knockout mice, as evidenced by caspase-3 activity. Consistent with this, expressions of vascular endothelial growth factor receptor-2 and platelet endothelial cell adhesion molecule-1 on endothelial cells were decreased in the adiponectin-knockout mice. Finally, adenovirus-mediated adiponectin supplementation ameliorated the emphysematous phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Adiponectin-knockout mice develop progressive chronic obstructive pulmonary disease\u2013like phenotype with systemic inflammation and extrapulmonary phenotypes. Hypoadiponectinemia could thus play a critical role in the progression of chronic obstructive pulmonary disease and concomitant comorbidities through endothelial dysfunction. Together, adiponectin could be a novel target for chronic obstructive pulmonary disease therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201007-1091oc","type":"journal-article","created":{"date-parts":[[2011,1,14]],"date-time":"2011-01-14T22:32:52Z","timestamp":1295044372000},"page":"1164-1175","source":"Crossref","is-referenced-by-count":60,"title":["Involvement of Endothelial Apoptosis Underlying Chronic Obstructive Pulmonary Disease\u2013like Phenotype in Adiponectin-null Mice: Implications for Therapy"],"prefix":"10.1093","volume":"183","author":[{"given":"Kaori","family":"Nakanishi","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Allergy and Rheumatic Diseases; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Allergy and Rheumatic Diseases; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Tetsumoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Allergy and Rheumatic Diseases; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Allergy and Rheumatic Diseases; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Tsujino","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Allergy and Rheumatic Diseases; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanako","family":"Kuhara","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Allergy and Rheumatic Diseases; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingji","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Allergy and Rheumatic Diseases; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Nagatomo","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Allergy and Rheumatic Diseases; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kida","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Allergy and Rheumatic Diseases; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Goya","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Allergy and Rheumatic Diseases; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kijima","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Allergy and Rheumatic Diseases; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norikazu","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Funahashi","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iichiro","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Tachibana","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Allergy and Rheumatic Diseases; 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