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Expression profiling analysis of long noncoding RNAs in a mouse model of ventilator-induced lung injury indicating potential roles in inflammation
Authors:Nan-Nan Zhang  Yi Zhang  Lu Wang  Jin-Gen Xia  Shun-Tao Liang  Yan Wang  Zhi-Zhi Wang  Xu Huang  Min Li  Hui Zeng  Qing-Yuan Zhan
Affiliation:1. Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China

Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

National Clinical Research Center for Respiratory Diseases, Beijing, China

Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China;2. Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China

Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

National Clinical Research Center for Respiratory Diseases, Beijing, China;3. Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China;4. Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China;5. Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China

Abstract:The key regulators of inflammation underlying ventilator-induced lung injury (VILI) remain poorly defined. Long noncoding RNAs (lncRNAs) have been implicated in the inflammatory response of many diseases; however, their roles in VILI remain unclear. We, therefore, performed transcriptome profiling of lncRNA and messenger RNA (mRNA) using RNA sequencing in lungs collected from mice model of VILI and control groups. Gene expression was analyzed through RNA sequencing and quantitative reverse transctiption polymerase chain reaction. A comprehensive bioinformatics analysis was used to characterize the expression profiles and relevant biological functions and for multiple comparisons among the controls and the injury models at different time points. Finally, lncRNA-mRNA coexpression networks were constructed and dysregulated lncRNAs were analyzed functionally. The mRNA transcript profiling, coexpression network analysis, and functional analysis of altered lncRNAs indicated enrichment in the regulation of immune system/inflammation processes, response to stress, and inflammatory pathways. We identified the lncRNA Gm43181 might be related to lung damage and neutrophil activation via chemokine receptor chemokine (C-X-C) receptor 2. In summary, our study provides an identification of aberrant lncRNA alterations involved in inflammation upon VILI, and lncRNA-mediated regulatory patterns may contribute to VILI inflammation.
Keywords:inflammation  long noncoding RNA  RNA sequencing  ventilator-induced lung injury
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