{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:45:38Z","timestamp":1788173138250,"version":"build-2803163510"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2017YFD0501200"],"award-info":[{"award-number":["2017YFD0501200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2017YFD0501305"],"award-info":[{"award-number":["2017YFD0501305"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    <jats:italic>Clonorchis sinensis<\/jats:italic>\n                    is an important food-borne zoonotic parasite which has been linked to biliary fibrosis and cholangiocarcinoma. However, the details of the pathogenesis of\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>sinensis<\/jats:italic>\n                    were unclear. To explore the role and regulatory mechanism of toll-like receptor 2 (TLR2) in\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>sinensis-<\/jats:italic>\n                    induced biliary fibrosis, we established the\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>sinensis<\/jats:italic>\n                    -infected C57BL\/6 mouse model with\n                    <jats:italic>\n                      TLR2\n                      <jats:sup>-\/-<\/jats:sup>\n                    <\/jats:italic>\n                    and wild type (WT) mice. The mortality rate, liver lesions, TLR2 and TGF-\u03b21 expression, phosphorylation of Smad2\/3, AKT, p38, ERK and p65, and cytokine productions were analyzed. Furthermore, similar parameters were examined in mouse biliary epithelial cells (BECs) co-cultured with\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>sinensis<\/jats:italic>\n                    excretory\/secretory proteins (ESPs). The results showed that TLR2 expression was enhanced significantly in\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>sinensis<\/jats:italic>\n                    -infected WT mice and mouse BECs.\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>sinensis<\/jats:italic>\n                    -infected\n                    <jats:italic>\n                      TLR2\n                      <jats:sup>-\/-<\/jats:sup>\n                    <\/jats:italic>\n                    mice exhibited an increased weight and a decreased mortality rate; significantly alleviated liver lesions and biliary fibrosis, reduced numbers of myofibroblasts; decreased expression of TGF-\u03b21 and phosphorylation level of AKT, p38 and Smad2\/3; significantly decreased production of IL-6, TNF-\u03b1 and IL-4, while increased production of IFN-\u03b3 compared with\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>sinensis<\/jats:italic>\n                    -infected WT mice. Furthermore,\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>sinensis<\/jats:italic>\n                    ESPs could activate TLR2-mediated AKT and p38 pathways to increase the production of IL-6 in mouse BECs. In conclusion, these data indicate that\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>sinensis<\/jats:italic>\n                    infection activated TGF-\u03b21-Smad2\/3 through TLR2-mediated AKT and p38 pathways to promote IL-6 production, which resulted in myofibroblast activation and aggravating biliary fibrosis in mice.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0011062","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T13:25:45Z","timestamp":1674566745000},"page":"e0011062","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Clonorchis sinensis aggravates biliary fibrosis through promoting IL-6 production via toll-like receptor 2-mediated AKT and p38 signal 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