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Hepatic stellate cells (HSCs) activation is a key process in initiating hepatic fibrosis and can be ameliorated by the administration of probiotic strains. This study hypothesized that LAB strains (<jats:italic>Lactiplantibacillus plantarum<\/jats:italic>, <jats:italic>Lactobacillus brevis<\/jats:italic>, and <jats:italic>Weissella cibaria<\/jats:italic>) might attenuate pro-fibrogenic cytokine TGF-\u03b2 mediated HSCs activation and induce collagen deposition, expression of other fibrogenic\/inflammatory markers, autophagy, and apoptotic processes <jats:italic>in vitro<\/jats:italic>. Few studies have evaluated the probiotic effects against fibrogenesis <jats:italic>in vitro<\/jats:italic>. In this study, TGF-\u03b2 exposure increased collagen deposition in LX-2 cells, but this increase was diminished when the cells were pretreated with LAB strains before TGF-\u03b2 stimulation. TGF-\u03b2 not only increased collagen deposition, but it also significantly upregulated the mRNA levels of Col1A1, alpha-smooth muscle actin (\u03b1-SMA), matrix metalloproteinases-2 (MMP-2), IL-6, CXCL-8, CCL2, and IL-1\u03b2 in LX-2 cells. Pretreatment of the cells with LAB strains counteracted the TGF-\u03b2-induced pro-fibrogenic and inflammatory markers by modulating SMAD-dependent and SMAD-independent TGF-\u03b2 signaling. In addition, LX-2 cells exposed to TGF-\u03b2 induced the autophagic and apoptotic associated proteins that were also positively regulated by the LAB strains. These findings suggest that LAB can attenuate TGF-\u03b2 signaling that is associated with liver fibrogenesis.<\/jats:p>","DOI":"10.1371\/journal.pone.0262767","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T18:29:30Z","timestamp":1642703370000},"page":"e0262767","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":34,"title":["Probiotics counteract the expression of hepatic profibrotic genes via the attenuation of TGF-\u03b2\/SMAD signaling and autophagy in hepatic stellate cells"],"prefix":"10.1371","volume":"17","author":[{"given":"Paulraj","family":"Kanmani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1038-0142","authenticated-orcid":true,"given":"Hojun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"issue":"3","key":"pone.0262767.ref001","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1111\/cas.13497","article-title":"Pretreatment with probiotic Bifico ameliorates colitis-associated cancer in mice: Transcriptome and gut flora profiling","volume":"109","author":"H Song","year":"2018","journal-title":"Cancer Sci"},{"key":"pone.0262767.ref002","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1007\/s00394-018-1785-z","article-title":"An open-label, randomized, placebo-controlled study on the effectiveness of a novel probiotics administration protocol (ProbioticCKD) in patients with mild renal insufficiency (stage 3a of CKD).","volume":"58","author":"M Simeoni","year":"2019","journal-title":"Eur J Nutr"},{"key":"pone.0262767.ref003","doi-asserted-by":"crossref","first-page":"112183","DOI":"10.1016\/j.bbr.2019.112183","article-title":"Sepehri G, Salami M. 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