Autocrine transforming growth factor-β/activin A-Smad signaling induces hepatic progenitor cells undergoing partial epithelial-mesenchymal transition states

doi:10.1016/j.biochi.2018.03.003

. 2018 May:148:87-98.

doi: 10.1016/j.biochi.2018.03.003. Epub 2018 Mar 13.

Autocrine transforming growth factor-β/activin A-Smad signaling induces hepatic progenitor cells undergoing partial epithelial-mesenchymal transition states

Yu Wu¹, Ze-Yang Ding², Guan-Nan Jin³, Yi-Xiao Xiong⁴, Bin Yu⁵, Yi-Min Sun⁶, Wei Wang⁷, Hui-Fang Liang⁸, Bixiang Zhang⁹, Xiao-Ping Chen¹⁰

Affiliations

¹ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: wuyu@hust.edu.cn.
² Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: zyding@tjh.tjmu.edu.cn.
³ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: jgnlh@163.com.
⁴ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: xiongyixiao@hust.edu.cn.
⁵ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: yaleo1990@hotmail.com.
⁶ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: sunyimin224@163.com.
⁷ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: freeskywang@163.com.
⁸ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: lianghuifang1997@163.com.
⁹ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: bixiangzhang@tjh.tjmu.edu.cn.
¹⁰ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: xpchen@tjh.tjmu.edu.cn.

PMID: 29544731
DOI: 10.1016/j.biochi.2018.03.003

Autocrine transforming growth factor-β/activin A-Smad signaling induces hepatic progenitor cells undergoing partial epithelial-mesenchymal transition states

Yu Wu et al. Biochimie. 2018 May.

. 2018 May:148:87-98.

doi: 10.1016/j.biochi.2018.03.003. Epub 2018 Mar 13.

Authors

Yu Wu¹, Ze-Yang Ding², Guan-Nan Jin³, Yi-Xiao Xiong⁴, Bin Yu⁵, Yi-Min Sun⁶, Wei Wang⁷, Hui-Fang Liang⁸, Bixiang Zhang⁹, Xiao-Ping Chen¹⁰

Affiliations

¹ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: wuyu@hust.edu.cn.
² Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: zyding@tjh.tjmu.edu.cn.
³ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: jgnlh@163.com.
⁴ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: xiongyixiao@hust.edu.cn.
⁵ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: yaleo1990@hotmail.com.
⁶ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: sunyimin224@163.com.
⁷ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: freeskywang@163.com.
⁸ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: lianghuifang1997@163.com.
⁹ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: bixiangzhang@tjh.tjmu.edu.cn.
¹⁰ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: xpchen@tjh.tjmu.edu.cn.

PMID: 29544731
DOI: 10.1016/j.biochi.2018.03.003

Abstract

Hepatic progenitor cells (HPCs) are a subpopulation of cells which was usually expanded in chronic liver injury and are contributed to liver regeneration through differentiating into hepatocytes and cholangiocytes. Epithelial-mesenchymal transition is a dynamic process which is important for the progression of liver fibrosis and cancer initiation. This study demonstrated that LE/6 and WB-F344 cells, both of which were HPC derived cell lines, were undergoing partial epithelial-mesenchymal transition states, which was indicated by the co-expression of epithelial markers (E-cadherin and zona occludin 1), and mesenchymal markers (vimentin, fibronectin, collagen 1and α-SMA). Furthermore, autocrine TGF-β and activin A signaling contributed to the maintenance of partial EMT in HPCs. In addition, Smad signaling, a classic downstream signaling cascade of both TGF-β and activin A, also participated in the partial EMT. These findings revealed the existence of partial EMT states in HPCs and confirmed some partial EMT related autocrine signaling cascades, and may help to further the understanding and explore the functional role of HPCs in the process of hepatic fibrosis and liver cancer initiation.

Keywords: Activin a; Hepatic progenitor cells; Partial epithelial-mesenchymal transition; Smad signaling; Transforming growth factor-β.

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Autocrine transforming growth factor-β/activin A-Smad signaling induces hepatic progenitor cells undergoing partial epithelial-mesenchymal transition states

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Autocrine transforming growth factor-β/activin A-Smad signaling induces hepatic progenitor cells undergoing partial epithelial-mesenchymal transition states

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