Open AccessIntegrated long non‐coding RNA analyses identify novel regulators of epithelial‐mesenchymal transition in the mouse model of pulmonary fibrosis
Author(s) -
Sun Hao,
Chen Junjie,
Qian Wenyi,
Kang Jiang,
Wang Jun,
Jiang Lei,
Qiao Li,
Chen Wei,
Zhang Jinsong
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12783
Subject(s) - epithelial–mesenchymal transition , idiopathic pulmonary fibrosis , pulmonary fibrosis , biology , cancer research , bleomycin , fibrosis , fibroblast , transcriptome , extracellular matrix , microrna , microarray analysis techniques , lung , pathology , microbiology and biotechnology , gene expression , gene , medicine , downregulation and upregulation , cell culture , genetics , chemotherapy
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 RNA s (lnc RNA s) and identified 513 up‐regulated and 204 down‐regulated lnc RNA s in paraquat‐induced fibrotic lung tissues. Gene ontology analysis revealed that the differentially expressed lnc RNA s 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 lnc RNA s, 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 lnc RNA in the regulation of EMT during lung fibrosis and provide potential avenues for the discovery of novel molecular markers and therapeutic targets for IPF .