Abstract
Liver fibrosis is a global public health problem, and the activation of hepatic stellate cells (HSCs) is the main driving force for liver fibrosis. However, the activation mechanism of HSCs is still not fully understood. In this study, we screened out 854 differentially expressed genes [Log2 fold change absolute: log2 FC(abs) ≥ 1] in activated LX-2 cells. Subsequently, we performed functional analyses of these differentially expressed genes. Gene Ontology enrichment analysis showed that the target genes were mainly enriched in processes such as positive regulation of cell migration involved in sprouting angiogenesis, negative regulation of keratinocyte proliferation, and nuclear inclusion bodies. Kyoto Encyclopedia of Gene and Genome signaling pathway enrichment analysis revealed that dysregulated genes were involved in signaling pathways such as pantothenate and coenzyme A biosynthesis and riboflavin metabolism. The microarray results were validated by reverse transcription-quantitative polymerase chain reaction, which indicated that the microarray results were reliable and that the tripartite motif containing 15 (TRIM15) had the highest absolute value of Log2FC. Additionally, the effect of TRIM15 on the proliferation, migration, and activation of LX-2 cells was assessed using overexpression plasmids and siRNA transfections. TRIM15 promoted the proliferation and migration of LX-2 cells and positively regulated the expression of α-smooth muscle actin and type I collagen. Collectively, the data revealed the gene expression profiles of quiescent and activated LX-2 cells and the involvement of TRIM15 in the activation of LX-2 cells. Hereby, TRIM15 could be a novel target of the HSC activation mechanism.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request for non‑commercial purposes, without breaching participant confidentiality.
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HL designed the study. JZ and YC performed the experiments and collected the data. YT and SC analyzed the data. All authors contributed to preparation of the manuscript and approved the final version.
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Zhang, J., Chen, Y., Tian, Y. et al. Knockdown of TRIM15 inhibits the activation of hepatic stellate cells. J Mol Histol 52, 839–848 (2021). https://doi.org/10.1007/s10735-021-09997-7
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DOI: https://doi.org/10.1007/s10735-021-09997-7