差异表达的长链非编码 RNA 在矽肺中的作用和 LOC103691771 在 TGF-β1 诱导的肌成纤维细胞分化中的作用。
Differential expression of lncRNAs during silicosis and the role of LOC103691771 in myofibroblast differentiation induced by TGF-β1.
机构信息
School of Public Health, North China University of Science and Technology, Tangshan, 063210 Hebei, China.
Hebei Key Laboratory for Organ Fibrosis Research, North China University of Science and Technology, Tangshan, 063210 Hebei, China.
出版信息
Biomed Pharmacother. 2020 May;125:109980. doi: 10.1016/j.biopha.2020.109980. Epub 2020 Feb 3.
OBJECTIVE
The role and molecular mechanism of long non-coding RNA (lncRNA)-related pathways in silicosis have not been elucidated clearly. The aims of this study were to evaluate the expression of lncRNAs during silica-induced pulmonary fibrosis and verify the function and molecular mechanism of LOC103691771 in myofibroblast differentiation induced by transforming growth factor-β1 (TGF-β1).
METHODS
RNA-sequencing was performed to assess differential expression of lncRNAs in control and silicotic rat lungs. Differential expression of lncRNAs was analyzed by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes to identify their biological roles. LOC103691771, LOC102549714, LOC102550137, LOC103693125, and LOC103692016 were selected to verify their expression by real-time PCR of silicotic rat lung tissue and lung fibroblasts stimulated by TGF-β1. Specific small interfering RNA and an LOC103691771 overexpression plasmid were used to analyze the molecular mechanism in myofibroblast differentiation induced by TGF-β1.
RESULT
A total of 306 lncRNAs were expressed differentially in silicotic rat lungs, including 224 upregulated and 82 downregulated lncRNAs. The expression of LOC103691771, LOC102549714 and LOC102550137 was upregulated, while the expression of LOC103693125 and LOC103692016 was downregulated in silicotic rat lungs and TGF-β1-induced fibroblast, which was consistent with the results of RNA-sequencing. Furthermore, LOC103691771 gene silencing attenuated myofibroblast differentiation, whereas LOC103691771 overexpression promoted myofibroblast differentiation via regulation of the TGF-β1-Smad2/3 signaling pathway.
CONCLUSION
Our findings revealed that differential expression of lncRNAs was related to the development of silicosis, and LOC103691771 played a major role in myofibroblast differentiation induced by TGF-β1, which may serve as a potential therapeutic target for silicosis.
目的
长链非编码 RNA（lncRNA）相关通路在矽肺中的作用和分子机制尚不清楚。本研究旨在评估 lncRNA 在二氧化硅诱导的肺纤维化过程中的表达情况，并验证 LOC103691771 在转化生长因子-β1（TGF-β1）诱导的肌成纤维细胞分化中的功能和分子机制。
方法
采用 RNA 测序技术评估对照和矽肺大鼠肺组织中 lncRNA 的差异表达。通过基因本体论和京都基因与基因组百科全书分析差异表达的 lncRNA，以确定其生物学功能。选择 LOC103691771、LOC102549714、LOC102550137、LOC103693125 和 LOC103692016 进行实时 PCR 验证矽肺大鼠肺组织和 TGF-β1 刺激的肺成纤维细胞中的表达情况。采用特异性小干扰 RNA 和 LOC103691771 过表达质粒分析 TGF-β1 诱导的肌成纤维细胞分化中的分子机制。
结果
在矽肺大鼠肺组织中，共检测到 306 个差异表达的 lncRNA，包括 224 个上调和 82 个下调的 lncRNA。LOC103691771、LOC102549714 和 LOC102550137 的表达在矽肺大鼠肺组织和 TGF-β1 诱导的成纤维细胞中上调，而 LOC103693125 和 LOC103692016 的表达下调，与 RNA 测序结果一致。此外，LOC103691771 基因沉默可减弱肌成纤维细胞分化，而 LOC103691771 过表达通过调节 TGF-β1-Smad2/3 信号通路促进肌成纤维细胞分化。
结论
本研究结果表明，lncRNA 的差异表达与矽肺的发生发展有关，LOC103691771 在 TGF-β1 诱导的肌成纤维细胞分化中起重要作用，可能成为矽肺的潜在治疗靶点。
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