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Exosomal MALAT1 Derived From Hepatic Cells Is Involved in the Activation of Hepatic Stellate Cells via miRNA-26b in Fibrosis Induced by Arsenite

45 Pages Posted: 16 Jan 2019

See all articles by Xiangyu Dai

Xiangyu Dai

Nanjing Medical University - Center for Global Health

Chao Chen

Zhengzhou University - Affiliated Cancer Hospital

Junchao Xue

Nanjing Medical University - Center for Global Health

Tian Xiao

Nanjing Medical University - Center for Global Health

Golam Mostofa

Dhaka Community Hospital Trust

Dapeng Wang

Guizhou Medical University (Guiyang Medical University)

Xiong Chen

Guizhou Medical University (Guiyang Medical University)

Hui Xu

Nanjing Medical University - Center for Global Health

Qian Sun

Nanjing Medical University - Center for Global Health

Junjie Li

Nanjing Medical University - Center for Global Health

Yongyue Wei

Nanjing Medical University - Department of Biostatistics

Feng Chen

Nanjing Medical University - Department of Biostatistics

Quazi Quamruzzaman

Dhaka Community Hospital Trust

Aihua Zhang

Guizhou Medical University (Guiyang Medical University)

Qizhan Liu

Nanjing Medical University - Center for Global Health

More...

Abstract

In the liver microenvironment, interactions among diverse types of hepatic cells are involved in liver fibrosis. In fibrotic tissues, exosomes act as transporters in intercellular communication. Long non-coding RNAs (lncRNAs) are involved in the activation of hepatic stellate cells (HSCs), which are participants in liver fibrosis. However, the functions of exosomal lncRNAs in liver fibrosis induced by arsenite are undefined. The purposes of the present study were (a) to determine if lncRNAs secreted from human hepatic (L-02) cells exposed to arsenite are shuttled to hepatic stellate LX-2 cells and (b) to establish their effects on LX-2 cells. In mice, MALAT1 was overexpressed in the progression of liver fibrosis induced by arsenite as well as in L-02 cells exposed to arsenite. Co-cultures with arsenite-treated L-02 cells induced the activation of LX-2 cells and overexpression of MALAT1. Arsenite-treated L-02 cells transported MALAT1 into LX-2 cells. Downregulation of MALAT1, which reduced the MALAT1 levels in exosomes derived from arsenite-treated L-02 cells, inhibited the activation of LX-2 cells. Additionally, exosomal MALAT1 derived from arsenite-treated L-02 cells promoted the activation of LX-2 cells via microRNA-26b regulation of COL1A2. Furthermore, circulating exosomal MALAT1 was up-regulated in people exposed to arsenite. In sum, exosomes derived from arsenite-treated hepatic cells transferred MALAT1 to HSCs, which induced their activation. These findings support the concept that, during liver fibrosis induced by arsenite, exosomal lncRNAs are involved in cell-cell communication.

Funding Statement: This work was supported by the Natural Science Foundations of China (81730089, 81430077); the National Key Research and Development Program of China (2016YFE0204900); the open project of Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment and Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, China (JX21817902/009); the open project of the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, China (GMU-2018-HJZ01); and the Priority Academic Program Development of Jiangsu Higher Education Institutions (2018).

Declaration of Interests: The authors declare they have no competing financial interests.

Ethics Approval Statement: Animals were treated humanely and with regard for alleviation of suffering according to a protocol approved by the Institutional Animal Care and Use committee (IACUC) of Nanjing Medical University.

Keywords: Arsenite; Exosomes; MALAT1; Liver fibrosis; HSCs

Suggested Citation

Dai, Xiangyu and Chen, Chao and Xue, Junchao and Xiao, Tian and Mostofa, Golam and Wang, Dapeng and Chen, Xiong and Xu, Hui and Sun, Qian and Li, Junjie and Wei, Yongyue and Chen, Feng and Quamruzzaman, Quazi and Zhang, Aihua and Liu, Qizhan, Exosomal MALAT1 Derived From Hepatic Cells Is Involved in the Activation of Hepatic Stellate Cells via miRNA-26b in Fibrosis Induced by Arsenite (January 14, 2019). Available at SSRN: https://ssrn.com/abstract=3315818

Xiangyu Dai

Nanjing Medical University - Center for Global Health

300 Guangzhou Road
Nanjing, Jiangsu 210029
China

Chao Chen

Zhengzhou University - Affiliated Cancer Hospital

Zhengzhou, Henan
China

Junchao Xue

Nanjing Medical University - Center for Global Health

300 Guangzhou Road
Nanjing, Jiangsu 210029
China

Tian Xiao

Nanjing Medical University - Center for Global Health

300 Guangzhou Road
Nanjing, Jiangsu 210029
China

Golam Mostofa

Dhaka Community Hospital Trust

Dhaka 1217, Bangladesh
India

Dapeng Wang

Guizhou Medical University (Guiyang Medical University)

Guiyang, Guizhou 550004
China

Xiong Chen

Guizhou Medical University (Guiyang Medical University)

Guiyang, Guizhou 550004
China

Hui Xu

Nanjing Medical University - Center for Global Health

300 Guangzhou Road
Nanjing, Jiangsu 210029
China

Qian Sun

Nanjing Medical University - Center for Global Health

300 Guangzhou Road
Nanjing, Jiangsu 210029
China

Junjie Li

Nanjing Medical University - Center for Global Health

300 Guangzhou Road
Nanjing, Jiangsu 210029
China

Yongyue Wei

Nanjing Medical University - Department of Biostatistics ( email )

Nanjing
China

Feng Chen

Nanjing Medical University - Department of Biostatistics ( email )

Nanjing
China

Quazi Quamruzzaman

Dhaka Community Hospital Trust

Dhaka 1217, Bangladesh
India

Aihua Zhang

Guizhou Medical University (Guiyang Medical University)

Guiyang, Guizhou 550004
China

Qizhan Liu (Contact Author)

Nanjing Medical University - Center for Global Health ( email )

300 Guangzhou Road
Nanjing, Jiangsu 210029
China

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