Differentially expressed mRNAs and lncRNAs shared between activated human hepatic stellate cells and nash fibrosis

Gerhard, Glenn S.; Davis, Bethany; Wu, Xiumei; Hanson, Amanda; Wilhelmsen, Danielle; Piras, Ignazio S.; Still, Christopher D.; Chu, Xin; Petrick, Anthony; DiStefano, Johanna K.

doi:10.1016/j.bbrep.2020.100753

Cited by 10 publications

(18 citation statements)

References 72 publications

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“…This same group had previously reported the RNA sequencing of primary HSCs taken from patients suffering from NAFLD (45). Comparison of the gene expression pro les of culture-activated LX-2 cells and primary NAFLD-associated HSCs revealed that 1,138 genes are differentially expressed in common (44).…”

Section: Discussionmentioning

confidence: 88%

“…Several studies have explored HSC activation at the transcriptomic level using various methods and cell lines (39)(40)(41)(42)(43)(44). The rst such study utilised microarray analysis to investigate the effects of cultureinduced activation (where HSCs activate over time on tissue culture plastic) on gene expression in LI90 cells, another immortalised human HSC line, when cultured on Matrigel (43).…”

Section: Discussionmentioning

confidence: 99%

“…Overall, the differential expression of 5,449 genes were detected and three genes which regulate the expression of connective tissue growth factor (CTGF), broblast growth factor 2 (FGF2) and netrin 4 (NTN4), each associated with HSC activation and liver brosis, were identi ed (39). The most recent study examining transcriptional regulation in HSCs used microarray analysis to investigate the differences between quiescent and culture-activated LX-2 cells, with MDI solution used to maintain quiescence (44). This study identi ed 3,424 differentially expressed genes with a fold change ≥ 2 (44).…”

Section: Discussionmentioning

confidence: 99%

“…The most recent study examining transcriptional regulation in HSCs used microarray analysis to investigate the differences between quiescent and culture-activated LX-2 cells, with MDI solution used to maintain quiescence (44). This study identi ed 3,424 differentially expressed genes with a fold change ≥ 2 (44). This same group had previously reported the RNA sequencing of primary HSCs taken from patients suffering from NAFLD (45).…”

Section: Discussionmentioning

confidence: 99%

“…As noted in the most recent study of Gerhard et al, the aim of all of these previous studies can be put simply as characterising the changes in gene expression that occur in HSCs during activation, and yet the ndings show a large amount of variation in both the identity and number of differentially expressed genes (44). It is clear that the methods used to provoke HSC quiescence or activation, and detect gene expression, as well as the speci c cell lines assayed, have a strong impact on the nal results (44). To our knowledge, the current study is the rst attempt to use RNA sequencing to investigate the changes in gene expression induced by TGF-β1 treatment in LX-2 cells.…”

Section: Discussionmentioning

confidence: 99%

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RNA Sequencing of LX-2 Cells Treated with TGF-β1 Identifies Genes Associated with Early Hepatic Stellate Cell Activation

Carson

Robinson

Ramm

et al. 2021

Preprint

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Hepatic stellate cells (HSCs) are liver-resident myofibroblast precursors. In chronic liver disease, HSC-derived myofibroblasts are responsible for the production of collagen and, as such, are generally associated with diseases characterised by hepatic fibrosis. HSCs undergo a process of "activation" in response to tissue damage or pathogen invasion, thereby assuming roles in extracellular matrix synthesis, wound healing, and pathogen defence. The process of HSC activation and collagen production is most commonly driven by the cytokine transforming growth factor-β1 (TGF-β1). To investigate the transcriptional impact of TGF-β1 signalling on liver myofibroblasts, RNA sequencing was used to quantitate the biological changes observed 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 known roles in influencing HSC activity, as well as those involved in fibrotic responses in other cell lines and tissues. Interestingly, genes with no currently characterised role in either HSC activation or fibrotic processes were also identified, including CIITA and SERPINB2. Further in silico analysis revealed the prominent signalling pathways downstream of TGF-β1 in LX-2 cells, which will be useful for improving the understanding of how this cytokine influences broader signalling pathways in the activation of HSCs. 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.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

RNA Sequencing of LX-2 Cells Treated with TGF-β1 Identifies Genes Associated with Early Hepatic Stellate Cell Activation

Carson

Robinson

Ramm

et al. 2021

Preprint

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Netrin-4: Focus on Its Role in Axon Guidance, Tissue Stability, Angiogenesis and Tumors

et al. 2022

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

et al. 2021

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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.

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Differentially expressed mRNAs and lncRNAs shared between activated human hepatic stellate cells and nash fibrosis

Cited by 10 publications

References 72 publications

RNA Sequencing of LX-2 Cells Treated with TGF-β1 Identifies Genes Associated with Early Hepatic Stellate Cell Activation

RNA Sequencing of LX-2 Cells Treated with TGF-β1 Identifies Genes Associated with Early Hepatic Stellate Cell Activation

Netrin-4: Focus on Its Role in Axon Guidance, Tissue Stability, Angiogenesis and Tumors

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

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