{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:38:21Z","timestamp":1789133901277,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["No. 2018R1D1A1B07040460 and 2019R1A2C1004636"],"award-info":[{"award-number":["No. 2018R1D1A1B07040460 and 2019R1A2C1004636"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by \u03b2-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, \u03b1-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-\u03b2-treated LX-2 cells. Furthermore, downstream of TGF-\u03b2, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl4)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&amp;E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl4-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-\u03b2\/Smad signaling pathway.<\/jats:p>","DOI":"10.3390\/ijms22042041","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T20:56:21Z","timestamp":1613681781000},"page":"2041","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-\u03b2\/Smad Signaling Pathway"],"prefix":"10.3390","volume":"22","author":[{"given":"Ji Hye","family":"Yang","sequence":"first","affiliation":[{"name":"College of Korean Medicine, Dongshin University, Naju, Jeollanam-do 58245, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1269-3804","authenticated-orcid":false,"given":"Sae Kwang","family":"Ku","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do 38610, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6295-0608","authenticated-orcid":false,"given":"IL Je","family":"Cho","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do 38610, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Je Hyeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Dyne Bio Inc. Seongnam-si, Gyeonggi-do 13209, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Su","family":"Na","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Dongshin University, Naju, Jeollanam-do 58245, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0761-3750","authenticated-orcid":false,"given":"Sung Hwan","family":"Ki","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chosun University, Seoseok-dong, Gwangju 61452, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis","volume":"115","author":"Bataller","year":"2005","journal-title":"J. Clin. 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