Статья

Pre–B-Cell Colony-enhancing Factor as a Potential Novel Biomarker in Acute Lung Injury

Shui Q. YeDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, MichiganBrett A. SimonDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, MichiganJames P. MaloneyDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, MichiganApril Zambelli-WeinerDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, MichiganLi GaoDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, MichiganAudrey V. GrantDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, MichiganR. Blaine EasleyDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, MichiganBryan J. McVerryDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, MichiganRubin M. TuderDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, MichiganTheodore J. StandifordDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, MichiganRoy G. BrowerDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, MichiganKathleen C. BarnesDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, MichiganJoe G. N. GarciaDivision of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Departments of Medicine, Anesthesiology and Critical Care Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, University of Michigan, Ann Arbor, Michigan

2004en

ABI

Аннотация

Although the pathogenic and genetic basis of acute lung injury (ALI) remains incompletely understood, the identification of novel ALI biomarkers holds promise for unique insights. Expression profiling in animal models of ALI (canine and murine) and human ALI detected significant expression of pre-B-cell colony-enhancing factor (PBEF), a gene not previously associated with lung pathophysiology. These results were validated by real-time polymerase chain reaction and immunohistochemistry studies, with PBEF protein levels significantly increased in both bronchoalveolar lavage fluid and serum of ALI models and in cytokine- or cyclic stretch-activated lung microvascular endothelium. We genotyped two PBEF single-nucleotide polymorphisms (SNPs) in a well characterized sample of white patients with sepsis-associated ALI, patients with severe sepsis, and healthy subjects and observed that carriers of the haplotype GC from SNPs T-1001G and C-1543T had a 7.7-fold higher risk of ALI (95% confidence interval 3.01-19.75, p < 0.001). The T variant from the SNP C-1543T resulted in a significant decrease in the transcription rate (1.8-fold; p < 0.01) by the reporter gene assay. Together, these results strongly indicate that PBEF is a potential novel biomarker in ALI and demonstrate the successful application of robust genomic technologies in the identification of candidate genes in complex lung disease.

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Идентификаторы

DOI: 10.1164/rccm.200404-563oc

Цитирования и источники

Цитирований: 2Использованных источников: 0

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