Focal Adhesion Kinase Regulates Hepatic Stellate Cell Activation and Liver Fibrosis

Abstract Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activati...

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Autores principales:	Xue-Ke Zhao, Lei Yu, Ming-Liang Cheng, Pulin Che, Yin-Ying Lu, Quan Zhang, Mao Mu, Hong Li, Li-Li Zhu, Juan-Juan Zhu, Meng Hu, Po Li, Yue-Dong Liang, Xin-Hua Luo, Yi-Ju Cheng, Zhi-Xiang Xu, Qiang Ding
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0be84a8d4f6043a6b8939f2069666e82
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spelling	oai:doaj.org-article:0be84a8d4f6043a6b8939f2069666e822021-12-02T11:40:43ZFocal Adhesion Kinase Regulates Hepatic Stellate Cell Activation and Liver Fibrosis10.1038/s41598-017-04317-02045-2322https://doaj.org/article/0be84a8d4f6043a6b8939f2069666e822017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04317-0https://doaj.org/toc/2045-2322Abstract Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activation is associated with increased expression of α-smooth muscle actin (α-SMA) and collagen in fibrotic live tissues. Transforming growth factor beta-1 (TGF-β1) induces FAK activation in a time and dose dependent manner. FAK activation precedes the α-SMA expression in HSCs. Inhibition of FAK activation blocks the α-SMA and collagen expression, and inhibits the formation of stress fibers in TGF-β1 treated HSCs. Furthermore, inhibition of FAK activation significantly reduces HSC migration and small GTPase activation, and induces apoptotic signaling in TGF-β1 treated HSCs. Importantly, FAK inhibitor attenuates liver fibrosis in vivo and significantly reduces collagen and α-SMA expression in an animal model of liver fibrosis. These data demonstrate that FAK plays an essential role in HSC activation and liver fibrosis progression, and FAK signaling pathway could be a potential target for liver fibrosis.Xue-Ke ZhaoLei YuMing-Liang ChengPulin CheYin-Ying LuQuan ZhangMao MuHong LiLi-Li ZhuJuan-Juan ZhuMeng HuPo LiYue-Dong LiangXin-Hua LuoYi-Ju ChengZhi-Xiang XuQiang DingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xue-Ke Zhao Lei Yu Ming-Liang Cheng Pulin Che Yin-Ying Lu Quan Zhang Mao Mu Hong Li Li-Li Zhu Juan-Juan Zhu Meng Hu Po Li Yue-Dong Liang Xin-Hua Luo Yi-Ju Cheng Zhi-Xiang Xu Qiang Ding Focal Adhesion Kinase Regulates Hepatic Stellate Cell Activation and Liver Fibrosis
description	Abstract Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activation is associated with increased expression of α-smooth muscle actin (α-SMA) and collagen in fibrotic live tissues. Transforming growth factor beta-1 (TGF-β1) induces FAK activation in a time and dose dependent manner. FAK activation precedes the α-SMA expression in HSCs. Inhibition of FAK activation blocks the α-SMA and collagen expression, and inhibits the formation of stress fibers in TGF-β1 treated HSCs. Furthermore, inhibition of FAK activation significantly reduces HSC migration and small GTPase activation, and induces apoptotic signaling in TGF-β1 treated HSCs. Importantly, FAK inhibitor attenuates liver fibrosis in vivo and significantly reduces collagen and α-SMA expression in an animal model of liver fibrosis. These data demonstrate that FAK plays an essential role in HSC activation and liver fibrosis progression, and FAK signaling pathway could be a potential target for liver fibrosis.
format	article
author	Xue-Ke Zhao Lei Yu Ming-Liang Cheng Pulin Che Yin-Ying Lu Quan Zhang Mao Mu Hong Li Li-Li Zhu Juan-Juan Zhu Meng Hu Po Li Yue-Dong Liang Xin-Hua Luo Yi-Ju Cheng Zhi-Xiang Xu Qiang Ding
author_facet	Xue-Ke Zhao Lei Yu Ming-Liang Cheng Pulin Che Yin-Ying Lu Quan Zhang Mao Mu Hong Li Li-Li Zhu Juan-Juan Zhu Meng Hu Po Li Yue-Dong Liang Xin-Hua Luo Yi-Ju Cheng Zhi-Xiang Xu Qiang Ding
author_sort	Xue-Ke Zhao
title	Focal Adhesion Kinase Regulates Hepatic Stellate Cell Activation and Liver Fibrosis
title_short	Focal Adhesion Kinase Regulates Hepatic Stellate Cell Activation and Liver Fibrosis
title_full	Focal Adhesion Kinase Regulates Hepatic Stellate Cell Activation and Liver Fibrosis
title_fullStr	Focal Adhesion Kinase Regulates Hepatic Stellate Cell Activation and Liver Fibrosis
title_full_unstemmed	Focal Adhesion Kinase Regulates Hepatic Stellate Cell Activation and Liver Fibrosis
title_sort	focal adhesion kinase regulates hepatic stellate cell activation and liver fibrosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0be84a8d4f6043a6b8939f2069666e82
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Focal Adhesion Kinase Regulates Hepatic Stellate Cell Activation and Liver Fibrosis

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