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

Content Provider	Europe PMC
Author	Carson, Jack P. Robinson, Mark W. Ramm, Grant A. Gobert, Geoffrey N.
Abstract	BackgroundHepatic 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 resultsRNA 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.ConclusionsIn 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.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC8604886&blobtype=pdf
ISSN	03014851
Journal	Molecular Biology Reports [Mol Biol Rep]
Volume Number	48
DOI	10.1007/s11033-021-06774-3
PubMed Central reference number	PMC8604886
Issue Number	12
PubMed reference number	34648138
e-ISSN	15734978
Language	English
Publisher	Springer Netherlands
Publisher Date	2021-10-14
Publisher Place	Dordrecht
Access Restriction	Open
Rights License	Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2021
Subject Keyword	Hepatic stellate cell LX-2 Transforming growth factor-β1 Fibrosis Chronic liver disease.
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine Molecular Biology