Bleomycin-induced Pulmonary Fibrosis in Mice Model: Analysis of Difference in Gene Expression Profile_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

XiangWeihong ¹ ,  WangLifeng ² , MiaoYunbo ² ,  FuEnqing ¹ , JinFaguang ¹

1. Departmat of Respiratory and Critical Care Medicine, Tandu Hospital, The Fourth Military Medical University, Xi'an, Shanxi, 710038, China;
2. ;

Corresponding?author：

WangLifeng, Email: lfwang@fmmu.edu.cn; FuEnqing, Email: fuenqing@sina.com

Keywords：

Bioinformatics; Pulmonary fibrosis; Gene profiles; BRB-Array tools

DOI：

10.7507/1671-6205.2015061

Video：

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Objective To investigate the molecular pathogenesis of pulmonary fibrosis induced by bleomycin in a murine model,and provide novel insights for clinical diagnosis and treatment. Methods From Gene Expression Omnibus,we downloaded microarray data extracted from experiments of bleomycin induced pulmonary fibrosis in wild-type mice. With BRB-Array Tools,differentially expressed genes at different time points during disease development were screened,selected and analyzed by DAVID software. Results BRB array analysis identified 45101 differentially expressed genes. After induction by bleomycin on 7^th day,1164 genes and 735 genes were significantly up-regulated and down-regulated (P<0.05,fold change>2),respectively. On 14^th day,731 genes and 390 genes were significantly up-regulated and down-regulated (P<0.05,fold change>2),respectively. DAVID analysis revealed that the up-regulated genes were significantly enriched in cell cycle,p53 signaling and chemokine signaling pathway,damaging reaction and collagen metabolism gene sets. While the down-regulated genes were enriched in the drug metabolism pathway gene set. Conclusions Bioinformatics methodologies are able to efficiently analyze microarray data and extract its underlying information,provide novel insights for major molecular events and shift of cell signaling pathway during pulmonary fibrosis progression,and furthermore,finding molecular markers for early diagnosis and therapeutic targets.

Citation： XiangWeihong, WangLifeng, MiaoYunbo, FuEnqing, JinFaguang. Bleomycin-induced Pulmonary Fibrosis in Mice Model: Analysis of Difference in Gene Expression Profile. Chinese Journal of Respiratory and Critical Care Medicine, 2015, 14(3): 242-249. doi: 10.7507/1671-6205.2015061 Copy

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15.	孫燕川.沙利度胺對博萊霉素致大鼠肺纖維化的干預作用及機制.學位論文,河北醫科大學,2011,49.
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1. ?Strieter RM,Mehrad B. New mechanisms of pulmonary fibrosis. Chest,2009,136:1364-1370.
2. Barkauskas CE,Noble PW. Cellular mechanisms of tissue fibrosis. 7. New insights into the cellular mechanisms of pulmonary fibrosis. Am J Physiol Cell Physiol,2014,306:C987-C996.
3. Fernandez IE,Eickelberg O. New cellular and molecular mechanisms of lung injury and fibrosis in idiopathic pulmonary fibrosis. Lancet,2012,380:680-688.
4. 弓孟春,張博,徐作軍.特發性肺纖維化發病率和患病率及臨床病程的人群研究.中華結核和呼吸雜志,2010,33:306.
5. Renzoni E,Srihari V,Sestini P. Pathogenesis of idiopathic pulmonary fibrosis:review of recent findings. F1000Prime Rep,2014,6:69.
6. Spagnolo P,Rossi G,Cavazza A. Pathogenesis of idiopathic pulmonary fibrosis and its clinical implications. Expert Rev Clin Immunol,2014,10:1005-1017.
7. Williamson JD,Sadofsky LR,Hart SP. The pathogenesis of bleomycin-induced lung injury in animals and its applicability to human idiopathic pulmonary fibrosis. Exp Lung Res,2015,41:57-73.
8. Simon R,Lam A,Li MC,et al. Analysis of gene expression data using BRB-ArrayTools. Cancer Inform,2007,3:11-17.
9. Kaminski N,Rosas IO. Gene expression profiling as a window into idiopathic pulmonary fibrosis pathogenesis:can we identify the right target genes? Proc Am Thorac Soc,2006,3:339-344.
10. Oga T,Matsuoka T,Yao C,et al. Prostaglandin F(2alpha) receptor signaling facilitates bleomycin-induced pulmonary fibrosis independently of transforming growth factor-beta. Nat Med,2009,15:1426-1430.
11. Ley B,Brown KK,Collard HR. Molecular biomarkers in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol,2014,307:L681-L691.
12. Peng R,Sridhar S,Tyagi G,et al. Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis:a model for "active" disease. PLoS One,2013,8:e59348.
13. 高建,劉干,李俊.肺成纖維細胞在肺纖維化進程中的作用.中國藥理學通報,2010,26:1125-1128.
14. 高蔚,張德平,華云峰.姜黃素對大鼠肺成纖維細胞增殖和凋亡的影響.實用醫學雜志,2008,24:2393-2396.
15. 孫燕川.沙利度胺對博萊霉素致大鼠肺纖維化的干預作用及機制.學位論文,河北醫科大學,2011,49.
16. Lilja-Maula L,Syrja P,Laurila HP,et al. Comparative study of transforming growth factor-beta signalling and regulatory molecules in human and canine idiopathic pulmonary fibrosis. J Comp Pathol,2014,150:399-407.
17. 趙永強,楚海燕,滕禮,等.博萊霉素誘導肺纖維化小鼠模型的建立及特征.疑難病雜志,2013,12:705-708.

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Bleomycin-induced Pulmonary Fibrosis in Mice Model: Analysis of Difference in Gene Expression Profile

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