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27 September 2019 MicroRNA-146a-5p Attenuates Fibrosis-related Molecules in Irradiated and TGF-beta1-Treated Human Hepatic Stellate Cells by Regulating PTPRA-SRC Signaling
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Abstract

MicroRNAs (miRNAs) have been shown to play a pivotal role in the pathogenesis and maintenance of liver fibrosis by altering expression of their downstream target genes. However, their role in radiation-induced liver fibrosis has not been assessed in detail. Here, we investigated the role of miR-146a-5p and the target gene in regulation of fibrosis-related markers in the human hepatic stellate cell line LX2. LX2 cells were stimulated with 8 Gy of X rays and various concentrations of TGF-β1 (0–5 ng/ml). Expression of α-SMA, collagen 1 and miR-146a-5p was evaluated. The MiR-146a-5p target gene predictions were performed using bioinformatics analysis and confirmed by dual-luciferase reporter experiment. The effect of miR-146a-5p and the involved target gene on the expression of these fibrogenic molecules was also assessed. Expression of α-SMA and collagen 1 were upregulated in response to radiation and/or TGF-β1 treatment and miR-146a-5p levels were altered in LX2 cells. Restoration of miR-146a-5p expression suppressed expression of α-SMA and collagen 1 in irradiated and TGF-β1-treated LX2 cells. Subsequent mechanism experiments revealed that miR-146a-5p overexpression inhibited PTPRA expression by binding to its 3′-untrans-lated region and reduced SRC activation. In addition, enhancement of PTPRA partially reversed the suppressive effect of miR-146a-5p on α-SMA and collagen 1 expression in LX2 cells. In conclusion, miR-146a-5p may negatively regulate the PTPRA-SRC signaling to inhibit expression of fibrosis-related markers in irradiated and TGF-β1-stimulated LX2 cells.

©2019 by Radiation Research Society. All rights of reproduction in any form reserved.
Bao-Ying Yuan, Yu-Han Chen, Zhi-Feng Wu, Yuan Zhuang, Gen-Wen Chen, Li Zhang, Hai-Ge Zhang, Jason Chia-Hsien Cheng, Qin Lin, and Zhao-Chong Zeng "MicroRNA-146a-5p Attenuates Fibrosis-related Molecules in Irradiated and TGF-beta1-Treated Human Hepatic Stellate Cells by Regulating PTPRA-SRC Signaling," Radiation Research 192(6), 621-629, (27 September 2019). https://doi.org/10.1667/RR15401.1
Received: 3 April 2019; Accepted: 13 September 2019; Published: 27 September 2019
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