{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:33:32Z","timestamp":1791408812722,"version":"4.3.3"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yin Shu-Tien Foundation Development and Construction Plan of the College of Medicine, National Yang Ming Chiao Tung University","award":["113Q159604"],"award-info":[{"award-number":["113Q159604"]}]},{"name":"Yin Shu-Tien Foundation Development and Construction Plan of the College of Medicine, National Yang Ming Chiao Tung University","award":["114Q153602"],"award-info":[{"award-number":["114Q153602"]}]},{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"crossref","award":["KSVGH111-13"],"award-info":[{"award-number":["KSVGH111-13"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"crossref","award":["KSVGH114-015"],"award-info":[{"award-number":["KSVGH114-015"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"crossref","award":["KSVGH114-081"],"award-info":[{"award-number":["KSVGH114-081"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute respiratory distress syndrome (ARDS) is a fatal inflammatory lung disorder with few effective treatments. Hyaluronan (HA), a major extracellular matrix component, exhibits diverse biological activities depending on its molecular weight. This study aimed to evaluate the therapeutic potential of HA of various molecular weights in a rat model of ARDS. ARDS was induced in rats via the intratracheal instillation of 5 mg of bleomycin. Seven days later, when ARDS symptoms developed, low (LHA), medium (MHA), high (HHA), and mixed (MIX HA) hyaluronan were intratracheally administered seven times from Days 7 to 28. On Day 7, arterial oxygen saturation (SpO2) and the partial pressure of oxygen (PaO2) decreased, carbon dioxide levels increased, the respiratory rate increased, and extensive lung cell infiltration was observed, confirming successful ARDS induction. LHA and MIX HA improved the SpO2 and PaO2, and the latter increased lung and alveolar volume, reduced infiltration, and normalized breathing. All HA types attenuated collagen deposition and M1 macrophage activity, while MIX HA enhanced M2 polarization and upregulated MMP-2, MMP-9, and TLR-4. LHA increased VEGF and EGF expression. These findings demonstrate that different-weight HAs provide partial ARDS protection via distinct mechanisms. MIX HA shows synergistic effects, restoring and improving lung structure and function, respectively, representing a promising ARDS therapy.<\/jats:p>","DOI":"10.3390\/ijms27020580","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T13:49:46Z","timestamp":1767707386000},"page":"580","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hyaluronan of Different Molecular Weights Exerts Distinct Therapeutic Effects on Bleomycin-Induced Acute Respiratory Distress Syndrome"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6186-8972","authenticated-orcid":false,"given":"Shu-Ting","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yu","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsui-Ling","family":"Ko","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Hsiang","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Cheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-An","family":"Chu","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan"},{"name":"Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"},{"name":"School of Nursing, Fooyin University, Kaohsiung 831301, Taiwan"},{"name":"Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung 821, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4754-6006","authenticated-orcid":false,"given":"Yu-Show","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/HP.0b013e31826386ef","article-title":"A preclinical rodent model of radiation-induced lung injury for medical countermeasure screening in accordance with the FDA animal rule","volume":"103","author":"Jackson","year":"2012","journal-title":"Health Phys."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/1465-9921-6-112","article-title":"The role of pro- and anti-inflammatory responses in silica-induced lung fibrosis","volume":"6","author":"Barbarin","year":"2005","journal-title":"Respir. 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