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RNA sequencing of LX-2 cells treated with TGF-β1 identifies genes associated with hepatic stellate cell activation

Authors :
Mark W. Robinson
Geoffrey N. Gobert
Grant A. Ramm
Jack P. Carson
Source :
Molecular Biology Reports, Carson, J, Robinson, M, Ramm, G A & Gobert, G 2021, ' RNA sequencing of LX-2 cells treated with TGF-β1 identifies genes associated with hepatic stellate cell activation ', Molecular Biology Reports . https://doi.org/10.1007/s11033-021-06774-3
Publication Year :
2021
Publisher :
Springer Science and Business Media LLC, 2021.

Abstract

Background Hepatic stellate cells (HSCs) are liver-resident myofibroblast precursors responsible for the production of collagen and maintenance of the hepatic extracellular matrix (ECM). As such, they are generally associated with fibrotic liver diseases. HSCs become “activated” in response to tissue damage or pathogen invasion, a process most commonly driven by transforming growth factor-β1 (TGF-β1). Despite this, the full extent of TGF-β1 signalling in these cells is poorly understood. Clarifying the range and diversity of this signalling will further improve our understanding of the process of HSC activation. Methods and results RNA sequencing was used to quantitate the transcriptomic changes induced in LX-2 cells, an activated human HSC line, following TGF-b1 treatment. In total, 5,258 genes were found to be significantly differentially expressed with a false discovery rate cut-off of < 0.1. The topmost deregulated of these genes included those with no currently characterised role in either HSC activation or fibrotic processes, including CIITA and SERPINB2. In silico analysis revealed the prominent signalling pathways downstream of TGF-β1 in LX-2 cells. Conclusions In this study, we describe the genes and signalling pathways significantly deregulated in LX-2 cells following TGF-β1 treatment. We identified several highly deregulated genes with no currently characterised role in HSC activation, which may represent novel mediators of fibrotic responses in HSCs or the liver macroenvironment. This work may be of use in the identification of new markers of liver fibrosis and could provide insight into prospective genes or pathways that might be targeted for the amelioration of fibrotic liver disease in the future.

Details

ISSN :
15734978 and 03014851
Volume :
48
Database :
OpenAIRE
Journal :
Molecular Biology Reports
Accession number :
edsair.doi.dedup.....64b5a72ff9767ec9874c146ecf713c13