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However, the significance of Wnt2b in the pathogenesis of fibrosis-related liver diseases remains undefined. Here, we report that Wnt2b was highly expressed in the fibrotic liver tissues, exhibiting protective effects against activation of hepatic stellate cells (HSCs) and fibrosis progression. We identified a negative regulation of Wnt2b on the toll-like receptor 4 (TLR4) activation-mediated pro-fibrogenic effects. Wnt2b was shown not only to directly suppress LPS-induced HSCs activation, but also to inhibit TLR4-enhanced the sensitivity of HSCs to transforming growth factor beta (TGF-\u03b2). Mechanistic study showed that Wnt2b suppresses TLR4 signaling through inhibiting the expression of TLR4 as well as the activation of NF-\u03baB and MAPKs. These findings provided new insights into the pathophysiology of liver fibrosis by characterizing Wnt2b as a novel endogenous suppressor of TLR4 signaling, maintaining tissue homeostasis during the early stage of hepatic fibrosis-associated liver diseases.<\/jats:p>","DOI":"10.1038\/s41598-017-04374-5","type":"journal-article","created":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T10:14:48Z","timestamp":1497521688000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Wnt2b attenuates HSCs activation and liver fibrosis through negative regulating TLR4 signaling"],"prefix":"10.1038","volume":"7","author":[{"given":"Yi","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuju","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,21]]},"reference":[{"key":"4374_CR1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nri3623","volume":"14","author":"A Pellicoro","year":"2014","unstructured":"Pellicoro, A., Ramachandran, P., Iredale, J. P. & Fallowfield, J. A. Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nature reviews. Immunology \n                           14, 181\u2013194, doi:10.1038\/nri3623 (2014).","journal-title":"Nature reviews. Immunology"},{"key":"4374_CR2","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/nrgastro.2010.97","volume":"7","author":"SL Friedman","year":"2010","unstructured":"Friedman, S. L. Evolving challenges in hepatic fibrosis. Nature reviews. Gastroenterology & hepatology \n                           7, 425\u2013436, doi:10.1038\/nrgastro.2010.97 (2010).","journal-title":"Nature reviews. Gastroenterology & hepatology"},{"key":"4374_CR3","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1172\/JCI66028","volume":"123","author":"D Schuppan","year":"2013","unstructured":"Schuppan, D. & Kim, Y. O. Evolving therapies for liver fibrosis. 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