title: Integrated long non-coding RNA analyses identify novel regulators of epithelial-mesenchymal transition in the mouse model of pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease characterized by aberrant accumulation of fibroblast population and deposition of extra cellular matrix. Increasing evidence support that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells is a critical process in the pathogenesis of IPF. Although delivery of bleomycin to induce acute lung injury is the most well-studied animal model of pulmonary fibrosis, there is considerable interest to pursue other models to understand the common and/or specific pathological mechanisms. In this study, we established a mouse model of pulmonary injury and progressive interstitial fibrosis via intraperitoneal injection of paraquat, a widely used herbicide known to cause pulmonary fibrosis in human. Using transcriptome sequencing and microarray analysis, we profiled expression of long non-coding RNAs (lncRNAs) and identified 513 up-regulated and 204 down-regulated lncRNAs in paraquat-induced fibrotic lung tissues. Gene ontology analysis revealed that the differentially expressed lncRNAs are implicated in cell differentiation, epithelium morphogenesis and wound healing, pathways closely associated with EMT. Furthermore, we identified the evolutionally conserved target genes of two up-regulated lncRNAs, uc.77 and 2700086A05Rik, as Zeb2 and Hoxa3, respectively, both of which are important modulators of EMT. Consistently, overexpression of uc.77 or 2700086A05Rik in human lung epithelial cells induced EMT as demonstrated by changes in gene and protein expression of various EMT markers and cell morphology. Collectively, our results uncovered a crucial role of lncRNA in the regulation of EMT during lung fibrosis and provide potential avenues for the discovery of novel molecular markers and therapeutic targets for IPF.
authors.affiliation: Department of Emergency, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Emergency, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.|Department of Intensive Care Unit, Yixing People's Hospital, Yixing, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Lab of Modern Toxicology, Ministry of Education and Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qian
authors.affiliation: Department of Emergency, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Kang
authors.affiliation: Key Lab of Modern Toxicology, Ministry of Education and Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Emergency, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Emergency, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Emergency, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020869:Gene Expression Profiling; D063990:Gene Ontology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000473:pathology; D008807:Mice, Inbred BALB C; D010269:Paraquat; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D010269:Paraquat
keywords: epithelial-mesenchymal transition; long non-coding RNA; paraquat; pulmonary fibrosis
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