A systems approach to mapping transcriptional networks controlling surfactant homeostasis

BMC Genomics

Research Article

Pooja Kadambi¹  Minlu Zhang²  Long J Lu²  Yanhua Wang³  Vrushank Dave³  Jeffrey A Whitsett³  Yan Xu⁴ 

[1] Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, USA;Division of Biomedical Informatics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA;Department of Computer Science, University of Cincinnati College of Medicine, Cincinnati, OH, USA;Division of Pulmonary Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA;Division of Pulmonary Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA;Division of Biomedical Informatics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA;

关键词: Sterol Regulatory Element Binding Protein;    Lung Maturation;    Surfactant Lipid;    Lung Lipid;    Pulmonary Alveolar Microlithiasis;   

DOI  :  10.1186/1471-2164-11-451

 received in 2009-10-05, accepted in 2010-07-26,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundPulmonary surfactant is required for lung function at birth and throughout life. Lung lipid and surfactant homeostasis requires regulation among multi-tiered processes, coordinating the synthesis of surfactant proteins and lipids, their assembly, trafficking, and storage in type II cells of the lung. The mechanisms regulating these interrelated processes are largely unknown.ResultsWe integrated mRNA microarray data with array independent knowledge using Gene Ontology (GO) similarity analysis, promoter motif searching, protein interaction and literature mining to elucidate genetic networks regulating lipid related biological processes in lung. A Transcription factor (TF) - target gene (TG) similarity matrix was generated by integrating data from different analytic methods. A scoring function was built to rank the likely TF-TG pairs. Using this strategy, we identified and verified critical components of a transcriptional network directing lipogenesis, lipid trafficking and surfactant homeostasis in the mouse lung.ConclusionsWithin the transcriptional network, SREBP, CEBPA, FOXA2, ETSF, GATA6 and IRF1 were identified as regulatory hubs displaying high connectivity. SREBP, FOXA2 and CEBPA together form a common core regulatory module that controls surfactant lipid homeostasis. The core module cooperates with other factors to regulate lipid metabolism and transport, cell growth and development, cell death and cell mediated immune response. Coordinated interactions of the TFs influence surfactant homeostasis and regulate lung function at birth.

【 授权许可】

CC BY   
© Xu et al; licensee BioMed Central Ltd. 2010