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Knockdown of TRIM15 inhibits the activation of hepatic stellate cells
Journal of Molecular Histology ( IF 3.2 ) Pub Date : 2021-06-17 , DOI: 10.1007/s10735-021-09997-7
Junpei Zhang 1 , Yin Chen 1 , Yi Tian 1 , Shiyao Chen 2 , Hailing Liu 1
Affiliation  

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.



中文翻译:

TRIM15的敲低抑制肝星状细胞的活化

肝纤维化是全球公共卫生问题,肝星状细胞(HSCs)的活化是肝纤维化的主要驱动力。然而,HSCs的激活机制仍不完全清楚。在这项研究中,我们筛选出 854 个差异表达基因 [Log 2绝对倍数变化:log2 FC(abs) ≥ 1] 在激活的 LX-2 细胞中。随后,我们对这些差异表达的基因进行了功能分析。基因本体富集分析表明,靶基因主要富集于细胞迁移的正调控参与萌芽血管生成、角质形成细胞增殖负调控、核包涵体等过程。京都基因百科全书和基因组信号通路富集分析表明,失调的基因参与了泛酸和辅酶A生物合成和核黄素代谢等信号通路。微阵列结果通过逆转录定量聚合酶链反应验证,2FC。此外,使用过表达质粒和 siRNA 转染评估了 TRIM15 对 LX-2 细胞增殖、迁移和活化的影响。TRIM15促进LX-2细胞的增殖和迁移,正向调节α-平滑肌肌动蛋白和I型胶原蛋白的表达。总的来说,数据揭示了静止和激活的 LX-2 细胞的基因表达谱以及 TRIM15 参与 LX-2 细胞的激活。因此,TRIM15 可能是 HSC 激活机制的新靶点。

更新日期:2021-06-18
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