Differential expression of lncRNAs during silicosis and the role of LOC103691771 in myofibroblast differentiation induced by TGF-β1

Wenchen Cai; Hong Xu; Bonan Zhang; Xuemin Gao; Shumin Li; Zhongqiu Wei; Shifeng Li; Na Mao; Fuyu Jin; Yaqian Li; Heliang Liu; Fang Yang

doi:10.1016/j.biopha.2020.109980

Differential expression of lncRNAs during silicosis and the role of LOC103691771 in myofibroblast differentiation induced by TGF-β1

Biomed Pharmacother. 2020 May:125:109980. doi: 10.1016/j.biopha.2020.109980. Epub 2020 Feb 3.

Authors

Wenchen Cai¹, Hong Xu², Bonan Zhang³, Xuemin Gao², Shumin Li³, Zhongqiu Wei³, Shifeng Li¹, Na Mao¹, Fuyu Jin³, Yaqian Li³, Heliang Liu¹, Fang Yang⁴

Affiliations

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.

PMID: 32028236
DOI: 10.1016/j.biopha.2020.109980

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.

Keywords: Fibroblast; LOC103691771; Myofibroblast; Silicosis; lncRNA.

MeSH terms

Animals
Cell Differentiation / drug effects
Cell Differentiation / genetics*
Cells, Cultured
Computational Biology / methods
Disease Models, Animal
Fibroblasts / metabolism
Gene Expression Profiling
Gene Expression Regulation* / drug effects
Gene Ontology
Myofibroblasts / cytology*
Myofibroblasts / metabolism*
RNA, Long Noncoding / genetics*
Rats
Signal Transduction / drug effects
Silicosis / genetics*
Silicosis / metabolism*
Silicosis / pathology
Smad2 Protein / metabolism
Transforming Growth Factor beta1 / metabolism

Substances

RNA, Long Noncoding
Smad2 Protein
Transforming Growth Factor beta1