{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:35:00Z","timestamp":1792859700431,"version":"4.5.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VHS Medical Center","award":["VHSMC17013"],"award-info":[{"award-number":["VHSMC17013"]}]},{"DOI":"10.13039\/501100002635","name":"Inha University","doi-asserted-by":"publisher","award":["63000-01"],"award-info":[{"award-number":["63000-01"]}],"id":[{"id":"10.13039\/501100002635","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>This study was undertaken to investigate the inhibitory effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Liver fibrosis was induced in Sprague-Dawley rats by injecting DMN intraperitoneally (at 10 mg\/kg of body weight) daily for three consecutive days per week for 4 weeks. To investigate the effect of GM-CSF on disease onset, GM-CSF (50 \u03bcg\/kg of body weight) was co-treated with DMN for 2 consecutive days per week for 4 weeks (4-week groups). To observe the effect of GM-CSF on the progression of liver fibrosis, GM-CSF was post-treated alone at 5\u20138 weeks after the 4 weeks of DMN injection (8-week groups). We found that DMN administration for 4 weeks produced molecular and pathological manifestations of liver fibrosis, that is, it increased the expressions of collagen type I, alpha-smooth muscle actin (\u03b1-SMA), and transforming growth factor-\u03b21 (TGF-\u03b21), and decreased peroxisome proliferator-activated receptor gamma (PPAR-\u03b3) expression. In addition, elevated serum levels of aspartate aminotransferase (AST), total bilirubin level (TBIL), and decreased albumin level (ALB) were observed. In both the 4-week and 8-week groups, GM-CSF clearly improved the pathological liver conditions in the gross and histological observations, and significantly recovered DMN-induced increases in AST and TBIL and decreases in ALB serum levels to normal. GM-CSF also significantly decreased DMN-induced increases in collagen type I, \u03b1-SMA, and TGF-\u03b21 and increased DMN-induced decreases in PPAR-\u03b3 expression. In the DMN groups, survival decreased continuously for 8 weeks after DMN treatment for the first 4 weeks. GM-CSF showed a survival benefit when co-treated for the first 4 weeks but a marginal effect when post-treated for 5\u20138 weeks. In conclusion, co-treatment of GM-CSF showed therapeutic effects on DMN-induced liver fibrosis and survival rates in rats, while post-treatment efficiently blocked liver fibrosis.<\/jats:p>","DOI":"10.1371\/journal.pone.0274126","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T17:26:00Z","timestamp":1662139560000},"page":"e0274126","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Granulocyte-macrophage colony-stimulating factor (GM-CSF) shows therapeutic effect on dimethylnitrosamine (DMN)-induced liver fibrosis in rats"],"prefix":"10.1371","volume":"17","author":[{"given":"Mrigendra Bir","family":"Karmacharya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binika","family":"Hada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Ra","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kil Hwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8996-8971","authenticated-orcid":true,"given":"Byung Hyune","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"issue":"1","key":"pone.0274126.ref001","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1172\/JCI88881","article-title":"Liver inflammation and fibrosis","volume":"127","author":"Y Koyama","year":"2017","journal-title":"J Clin Invest"},{"issue":"9963","key":"pone.0274126.ref002","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0140-6736(14)61682-2","article-title":"Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990\u20132013: a systematic analysis for the Global Burden of Disease Study 2013","volume":"385","author":"GBD 2013 Mortality and Causes of Death Collaborators","year":"2015","journal-title":"Lancet"},{"issue":"2","key":"pone.0274126.ref003","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis","volume":"115","author":"R Bataller","year":"2005","journal-title":"J Clin Invest"},{"key":"pone.0274126.ref004","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of liver fibrosis","volume":"6","author":"V Hernandez-Gea","year":"2011","journal-title":"Annu Rev Pathol"},{"issue":"4","key":"pone.0274126.ref005","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1159\/000374096","article-title":"Pathophysiology of liver fibrosis","volume":"33","author":"M. 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