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Thirty-two male Sprague\u2013Dawley rats were equally divided into four groups: control, TAA, TAA\u2009+\u2009SML 50\u00a0mg\/kg, and TAA\u2009+\u2009SML 100\u00a0mg\/kg groups. Liver functions and hepatic contents of glutathione (GSH) and malondialdehyde (MDA) were measured colorimetrically. Gene expressions of lysophosphatidic acid receptor (LPAR)-1 and -3, connective tissue growth factor (CTGF), transforming growth factor (TGF)-\u03b21, small mothers against decapentaplegic (Smad)-3 and -7, \u03b1-smooth muscle actin (\u03b1-SMA), and cytokeratin 19 (CK19) were analyzed by qRT-PCR. Moreover, phosphorylated Smad3 (pSmad3) was quantified by ELISA. Additionally, TGF-\u03b21, \u03b1-SMA, CK19, and vascular endothelial growth factor (VEGF) protein concentrations were semi-quantitatively analyzed by immunostaining of liver sections. SML treatment markedly improved liver index and liver functions. Moreover, SML protected against liver fibrosis in a dose-dependent manner as indicated by down-regulation of LPAR1, LPAR3, CTGF, TGF-\u03b21\/Smad3, and \u03b1-SMA expressions and a decrease in pSmad3 level, as well as an up-regulation of Smad7 expression. In addition, SML suppressed ductular reaction hinted by the decrease in CK19 expression. These results reveal the anti-fibrotic effect of SML against liver fibrosis that might be attributed to down-regulation of LPAR1\/3 expressions, inhibition of TGF-\u03b21\/Smad3 pathway, and ductular reaction.<\/jats:p>","DOI":"10.1007\/s00210-022-02259-7","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T05:02:31Z","timestamp":1654059751000},"page":"1003-1016","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Sesamol protects against liver fibrosis induced in rats by modulating lysophosphatidic acid receptor expression and TGF-\u03b2\/Smad3 signaling pathway"],"prefix":"10.1007","volume":"395","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6354-1152","authenticated-orcid":false,"given":"Nesma A. 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