The Research Center for Integrative Medicine, School of Fundamental Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
School of Chinese Materia Medical, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Int J Mol Sci. 2018 Feb 27;19(3):675. doi: 10.3390/ijms19030675.
Hepatic fibrosis is the main pathological basis for chronic cirrhosis, and activated hepatic stellate cells (HSCs) are the primary cells involved in liver fibrosis. Our study analyzed anti-fibrosis long noncoding RNAs (lncRNAs) in activated human HSCs (hHSCs). We performed RNA sequencing (RNA-seq) and bioinformatics analysis to determine whether lncRNA expression profile changes between hHSCs activation and quiescence. Eight differentially expressed (DE) lncRNAs and three pairs of co-expression lncRNAs-mRNAs were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). A total of 34146 DE lncRNAs were identified in this study. Via gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we found several DE lncRNAs regulated hHSC activation by participating in DNA bending/packaging complex, growth factor binding and the Hippo signaling pathway ( < 0.05). With lncRNA-mRNA co-expression analysis, three lncRNAs were identified to be associated with connective tissue growth factor (), fibroblast growth factor 2 () and netrin-4 (). The quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results of the eight DE lncRNAs and three pairs of co-expression lncRNAs-mRNAs were consistent with the RNA-seq data and previous reports. Several lncRNAs may serve as potential targets to reverse the progression of liver fibrosis. This study provides a first insight into lncRNA expression profile changes associated with activated human HSCs.
肝纤维化是慢性肝硬化的主要病理基础,活化的肝星状细胞(HSCs)是肝纤维化的主要细胞。我们的研究分析了活化的人 HSCs(hHSCs)中的抗纤维化长链非编码 RNA(lncRNA)。我们进行了 RNA 测序(RNA-seq)和生物信息学分析,以确定 hHSCs 激活和静止之间的 lncRNA 表达谱是否发生变化。通过定量实时聚合酶链反应(qRT-PCR)验证了 8 个差异表达(DE)lncRNA 和 3 对共表达 lncRNA-mRNA。本研究共鉴定出 34146 个 DE lncRNA。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析,我们发现一些 DE lncRNA 通过参与 DNA 弯曲/包装复合物、生长因子结合和 Hippo 信号通路来调节 hHSC 激活(<0.05)。通过 lncRNA-mRNA 共表达分析,鉴定出 3 个 lncRNA 与结缔组织生长因子()、成纤维细胞生长因子 2()和 netrin-4()相关。八个 DE lncRNA 和三个共表达 lncRNA-mRNA 的定量实时聚合酶链反应(qRT-PCR)结果与 RNA-seq 数据和以前的报道一致。一些 lncRNA 可能作为逆转肝纤维化进展的潜在靶点。本研究首次深入了解了与活化的人 HSCs 相关的 lncRNA 表达谱变化。