title: Lipopolysaccharide promotes pulmonary fibrosis in acute respiratory distress syndrome (ARDS) via lincRNA-p21 induced inhibition of Thy-1 expression.
abstract: Acute respiratory distress syndrome (ARDS) is a common clinical disorder characterized by pulmonary edema leading to acute lung damage and arterial hypoxemia. Pulmonary fibrosis is a progressive, fibrotic lung disorder, whose pathogenesis in ARDS remains speculative. LincRNA-p21 was a novel regulator of cell proliferation, apoptosis and DNA damage response. This study aims to investigate the effects and mechanism of lincRNA-p21 on pulmonary fibrosis in ARDS. Purified 10 mg/kg LPS was dropped into airways of C57BL/6 mice. Expression levels of lincRNA-p21 and Thy-1 were measured by real-time PCR or western blotting. Proliferation of lung fibroblasts was analyzed by BrdU incorporation assay. Lung and BAL collagen contents were estimated using colorimetric Sircol assay. LincRNA-p21 expression was time-dependently increased and Thy-1 expression was time-dependently reduced in a mouse model of ARDS and in LPS-treated lung fibroblasts. Meanwhile, lung fibroblast proliferation was also time-dependently elevated in LPS-treated lung fibroblasts. In addition, lung fibroblast proliferation could be promoted by lincRNA-p21 overexpression and LPS treatment, however, the elevated lung fibroblast proliferation was further abrogated by Thy-1 overexpression or lincRNA-p21 interference. And Thy-1 interference could elevate cell viability of lung fibroblasts and rescue the reduction of lung fibroblast proliferation induced by lincRNA-p21 interference. Moreover, lincRNA-p21 overexpression dramatically inhibited acetylation of H3 and H4 at the Thy-1 promoter and Thy-1 expression levels in HLF1 cells. Finally, lincRNA-p21 interference rescued LPS-induced increase of lung and BAL collagen contents. LincRNA-p21 could lead to pulmonary fibrosis in ARDS by inhibition of the expression of Thy-1.
authors.affiliation: Department of Emergency Medicine, Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China.
authors.forename: Wen-Qin
authors.initials: WQ
authors.lastname: Zhou
authors.affiliation: Department of Emergency Medicine, Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China.
authors.forename: Qiu-Ping
authors.initials: QP
authors.lastname: Shao
authors.affiliation: Department of Respiratory Medicine, Affiliated People's Hospital, Jiangsu University, 8, Dianli Road, Zhenjiang, 212002, Jiangsu, China. wj65812@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000096:biosynthesis*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D018800:Thy-1 Antigens / Q000096:biosynthesis*
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008070:Lipopolysaccharides; D062085:RNA, Long Noncoding; D018800:Thy-1 Antigens
keywords: ARDS; LincRNA-p21; Pulmonary fibrosis; Thy-1