Wenchen Cai1, Hong Xu2, Bonan Zhang3, Xuemin Gao2, Shumin Li3, Zhongqiu Wei3, Shifeng Li1, Na Mao1, Fuyu Jin3, Yaqian Li3, Heliang Liu1, Fang Yang4. 1. School of Public Health, North China University of Science and Technology, Tangshan, 063210 Hebei, China. 2. Hebei Key Laboratory for Organ Fibrosis Research, North China University of Science and Technology, Tangshan, 063210 Hebei, China. 3. Basic Medical College, North China University of Science and Technology, Tangshan, 063210 Hebei, China. 4. School of Public Health, North China University of Science and Technology, Tangshan, 063210 Hebei, China. Electronic address: fangyang@ncst.edu.cn.
Abstract
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.
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.