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17 December 2018 : Laboratory Research

The Combination of piR-823 and Eukaryotic Initiation Factor 3 B (EIF3B) Activates Hepatic Stellate Cells via Upregulating TGF-β1 in Liver Fibrogenesis

Xuechan Tang1ABCDEF, Xiaoli Xie1ACDE, Xin Wang1BCF, Yan Wang1AEF, Xiaoyu Jiang1ADF, Huiqing Jiang1ACD*

DOI: 10.12659/MSM.914222

Med Sci Monit 2018; 24: LBR9151-9165

Abstract

BACKGROUND: Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA, which has also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. piR-823 is increased in liver cirrhosis and hepatocellular carcinoma (HCC). However, there is no report on the function of piR-823 in hepatic stellate cells (HSCs) activation during hepatic fibrosis. The present study investigated the role of piR-823 in HSC activation.

MATERIAL AND METHODS: Liver fibrosis was induced in mice by carbon tetrachloride (CCL4) injection and bile duct ligation (BDL). The primary HSCs were isolated from mice and cultured. The expression of piR-823 was measured by real-time PCR. The effect of piR-823 on HSCs was evaluated by either sense sequence or antisense sequence of piR-823 carried by liposome. Proteins binding to piR-823 were assayed by RNA pull-down technique and liquid chromatography-mass spectrometry (LC-MS).

RESULTS: Our data for the first time show that piR-823 is significantly upregulated in activated HSCs. Overexpression of piR-823 promoted HSC proliferation, α-SMA and COL1a1 production, whereas inhibition of piR-823 suppressed the activity of HSCs. Interestingly, the combination of piR-823 and EIF3B promoted TGF-β1 expression.

CONCLUSIONS: Our data illustrate a novel mechanism of piR-823 in HSC activities. The combination of piR-823 and EIF3B increased TGF-β1 expression, which activates HSCs in liver fibrosis. piR-823 may be a new target in the treatment of liver fibrosis.

Keywords: Eukaryotic Initiation Factor-3, hepatic stellate cells, Liver Cirrhosis, RNA, Small Interfering, Transforming Growth Factor beta

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750