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Recent studies have revealed a new biological function of trehalose as an autophagy inducer. Thus far, there are few reports regarding the therapeutic effects of trehalose on fibrotic diseases. Therefore, we examined whether trehalose has anti-fibrotic effects on PF. PF was induced by intraperitoneal injection of chlorhexidine gluconate (CG). CG challenges induced the increase of peritoneal thickness, ColI\u03b1<jats:sub>1<\/jats:sub>mRNA expression and hydroxyproline content, all of which were significantly attenuated by trehalose. In addition, CG challenges induced a marked peritoneal accumulation of \u03b1-SMA<jats:sup>+<\/jats:sup>myofibroblasts that was reduced by trehalose. The number of Wt1<jats:sup>+<\/jats:sup>\u03b1-SMA<jats:sup>+<\/jats:sup>cells in the peritoneum increased following CG challenges, suggesting that a part of \u03b1-SMA<jats:sup>+<\/jats:sup>myofibroblasts were derived from peritoneal mesothelial cells (PMCs). The number of Wt1<jats:sup>+<\/jats:sup>\u03b1-SMA<jats:sup>+<\/jats:sup>cells was also suppressed by trehalose. Additionally, trehalose attenuated the increase of \u03b1-SMA and ColI\u03b1<jats:sub>1<\/jats:sub>mRNA expression induced by TGF-\u03b2<jats:sub>1<\/jats:sub>through Snail protein degradation, which was dependent on autophagy in PMCs. These results suggest that trehalose might be a novel therapeutic agent for PF through the induction of autophagy and the suppression of mesothelial-to-mesenchymal transition in PMCs.<\/jats:p>","DOI":"10.1038\/s41598-020-71230-4","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T10:03:50Z","timestamp":1598868230000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Trehalose ameliorates peritoneal fibrosis by promoting Snail degradation and inhibiting mesothelial-to-mesenchymal transition in mesothelial cells"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2416-2181","authenticated-orcid":false,"given":"Taito","family":"Miyake","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiko","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Tamai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Kamikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Miyagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisayuki","family":"Ogura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Yamamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Oshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiori","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Sagara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Shinozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Toyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kitajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Furuichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,31]]},"reference":[{"issue":"12","key":"71230_CR1","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1056\/NEJMra1300575","volume":"372","author":"DC Rockey","year":"2015","unstructured":"Rockey, D. 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