Wnt2b attenuates HSCs activation and liver fibrosis through negative regulating TLR4 signaling

Abstract The Wingless-type MMTV integration site family member 2b (Wnt2b) has been found to be a principal mediator of liver development and regeneration. However, the significance of Wnt2b in the pathogenesis of fibrosis-related liver diseases remains undefined. Here, we report that Wnt2b was highl...

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Autores principales:	Yi Yuan, Qiuju Han, Siyu Li, Zhigang Tian, Jian Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f6a27d00a0784ffb91e909997028a95d
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spelling	oai:doaj.org-article:f6a27d00a0784ffb91e909997028a95d2021-12-02T15:06:24ZWnt2b attenuates HSCs activation and liver fibrosis through negative regulating TLR4 signaling10.1038/s41598-017-04374-52045-2322https://doaj.org/article/f6a27d00a0784ffb91e909997028a95d2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04374-5https://doaj.org/toc/2045-2322Abstract The Wingless-type MMTV integration site family member 2b (Wnt2b) has been found to be a principal mediator of liver development and regeneration. 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-β). Mechanistic study showed that Wnt2b suppresses TLR4 signaling through inhibiting the expression of TLR4 as well as the activation of NF-κB 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.Yi YuanQiuju HanSiyu LiZhigang TianJian ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yi Yuan Qiuju Han Siyu Li Zhigang Tian Jian Zhang Wnt2b attenuates HSCs activation and liver fibrosis through negative regulating TLR4 signaling
description	Abstract The Wingless-type MMTV integration site family member 2b (Wnt2b) has been found to be a principal mediator of liver development and regeneration. 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-β). Mechanistic study showed that Wnt2b suppresses TLR4 signaling through inhibiting the expression of TLR4 as well as the activation of NF-κB 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.
format	article
author	Yi Yuan Qiuju Han Siyu Li Zhigang Tian Jian Zhang
author_facet	Yi Yuan Qiuju Han Siyu Li Zhigang Tian Jian Zhang
author_sort	Yi Yuan
title	Wnt2b attenuates HSCs activation and liver fibrosis through negative regulating TLR4 signaling
title_short	Wnt2b attenuates HSCs activation and liver fibrosis through negative regulating TLR4 signaling
title_full	Wnt2b attenuates HSCs activation and liver fibrosis through negative regulating TLR4 signaling
title_fullStr	Wnt2b attenuates HSCs activation and liver fibrosis through negative regulating TLR4 signaling
title_full_unstemmed	Wnt2b attenuates HSCs activation and liver fibrosis through negative regulating TLR4 signaling
title_sort	wnt2b attenuates hscs activation and liver fibrosis through negative regulating tlr4 signaling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f6a27d00a0784ffb91e909997028a95d
work_keys_str_mv	AT yiyuan wnt2battenuateshscsactivationandliverfibrosisthroughnegativeregulatingtlr4signaling AT qiujuhan wnt2battenuateshscsactivationandliverfibrosisthroughnegativeregulatingtlr4signaling AT siyuli wnt2battenuateshscsactivationandliverfibrosisthroughnegativeregulatingtlr4signaling AT zhigangtian wnt2battenuateshscsactivationandliverfibrosisthroughnegativeregulatingtlr4signaling AT jianzhang wnt2battenuateshscsactivationandliverfibrosisthroughnegativeregulatingtlr4signaling
_version_	1718388490030284800

Wnt2b attenuates HSCs activation and liver fibrosis through negative regulating TLR4 signaling

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