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Cell therapies, such as mesenchymal stem cell (MSC) and macrophage therapies, have attracted attention as potential strategies for mitigating liver fibrosis. Here, we evaluated the therapeutic effects of HMGB1 peptide synthesized from box A of high mobility group box 1 protein. Liver damage and fibrosis were evaluated using a carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)-induced cirrhosis mouse model. The effects of HMGB1 peptide against immune cells were evaluated by single-cell RNA-seq using liver tissues, and those against monocytes\/macrophages were further evaluated by in vitro analyses. Administration of HMGB1 peptide did not elicit a rapid response within 36 h, but attenuated liver damage after 1 week and suppressed fibrosis after 2 weeks. Fibrosis regression developed over time, despite continuous liver damage, suggesting that administration of this peptide could induce fibrolysis. In vitro analyses could not confirm a direct effect of HMGB1 peptide against monocyte\/macrophages. However, macrophages were the most affected immune cells in the liver, and the number of scar-associated macrophages (<jats:italic>Trem2<\/jats:italic>+<jats:italic>Cd9<\/jats:italic>+ cells) with anti-inflammatory markers increased in the liver following HMGB1 treatment, suggesting that indirect effects of monocytes\/macrophages were important for therapeutic efficacy. Overall, we established a new concept for cell-free therapy using HMGB1 peptide for cirrhosis through the induction of anti-inflammatory macrophages.<\/jats:p>","DOI":"10.1186\/s41232-021-00177-4","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:05:34Z","timestamp":1632701134000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice"],"prefix":"10.1186","volume":"41","author":[{"given":"Shunsuke","family":"Nojiri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsunori","family":"Tsuchiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Natsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suguru","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroteru","family":"Kamimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Motegi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Iwasawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeki","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Kumagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Kitayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Tung","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Ouchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Shimbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Takamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuto","family":"Tamai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Terai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,27]]},"reference":[{"issue":"2","key":"177_CR1","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/s00535-016-1258-1","volume":"52","author":"S Terai","year":"2017","unstructured":"Terai S, Tsuchiya A. Status of and candidates for cell therapy in liver cirrhosis: overcoming the \u201cpoint of no return\u201d in advanced liver cirrhosis. J Gastroenterol. 2017;52(2):129\u201340. https:\/\/doi.org\/10.1007\/s00535-016-1258-1.","journal-title":"J Gastroenterol."},{"issue":"1","key":"177_CR2","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s41232-017-0045-6","volume":"37","author":"A Tsuchiya","year":"2017","unstructured":"Tsuchiya A, Kojima Y, Ikarashi S, Seino S, Watanabe Y, Kawata Y, et al. Clinical trials using mesenchymal stem cells in liver diseases and inflammatory bowel diseases. Inflamm Regen. 2017;37(1):16. https:\/\/doi.org\/10.1186\/s41232-017-0045-6.","journal-title":"Inflamm Regen."},{"issue":"1","key":"177_CR3","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1172\/JCI200522675","volume":"115","author":"JS Duffield","year":"2005","unstructured":"Duffield JS, Forbes SJ, Constandinou CM, Clay S, Partolina M, Vuthoori S, et al. 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ST and KT received research funds from StemRIM Inc. TK and YO are employees of StemRIM Inc.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28"}}