Exosomal MALAT1 derived from hepatic cells is involved in the activation of hepatic stellate cells via miRNA-26b in fibrosis induced by arsenite. (November 2019)

• Record Type: Journal Article
• Authors: Dai, Xiangyu; Chen, Chao; Xue, Junchao; Xiao, Tian; Mostofa, Golam; Wang, Dapeng; Chen, Xiong; Xu, Hui; Sun, Qian; Li, Junjie; Wei, Yongyue; Chen, Feng; Quamruzzaman, Quazi; Zhang, Aihua; Liu, Qizhan
• Is Part Of: Toxicology letters. Volume 316(2019)
• Page Start: 73
• Page End: 84
• Publication Date: 2019-11
• Subjects: lncRNAs long non-coding RNAs -- HSCs hepatic stellate cells -- ECM extracellular matrix -- α-SMA α-smooth muscle actin -- MALAT1 metastasis-associated lung adenocarcinoma transcript 1 -- COL1A2 collagen type I alpha 2 -- HA hyaluronic acid -- PCIII procollagen type III -- qRT-PCR quantitative real-time PCR -- TEM transmission electron microscopy; Arsenite -- Exosomes -- MALAT1 -- Liver fibrosis -- HSCs; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2019.09.008
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: Arsenite increases the levels of MALAT1 during arsenite-induced liver fibrosis in mice. MALAT1 is shuttled from arsenite-treated liver cells to hepatic stellate cells via exosomes. Exosomal MALAT1 promotes the activation of hepatic stellate cells via miR-26b regulation of COL1A2 in hepatic stellate cells. 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.