Gene Expression Profiles of Acute Exacerbations of Idiopathic Pulmonary Fibrosis

• DOI: 10.1164/rccm.200810-1596oc
• Publication Date: 2009-04-11T00:45:06Z
• Authors: Kazuhisa Konishi; Kevin F. Gibson; Kathleen O. Lindell; Thomas J. Richards; Yingze Zhang; Rajiv Dhir; Michelle Bisceglia; Sebastien Gilbert; Samuel A. Yousem; Jin Woo Song; Dong Soon Kim; Naftali Kaminski
• Keywords: Genetic Markers; Male; alpha-Defensins; Gene Expression Profiling; Cyclin A; Middle Aged; Idiopathic Pulmonary Fibrosis; 3. Good health; 03 medical and health sciences; Dyspnea; 0302 clinical medicine; Case-Control Studies; Acute Disease; Humans; Female; RNA, Messenger; Cyclin A2; Aged; Oligonucleotide Array Sequence Analysis

Rationale: The molecular mechanisms underlying acute exacerbations of idiopathic pulmonary fibrosis (IPF) are poorly understood. We studied the global gene expression signature IPF.Objectives: To understand patterns IPF.Methods: RNA was extracted from 23 stable IPF lungs, 8 lungs with exacerbation (IPF-AEx), and 15 control used for hybridization on Agilent microarrays. Functional analysis genes performed Spotfire Genomica. Gene validations MMP1, MMP7, AGER, DEFA1–3, COL1A2, CCNA2 were by real-time quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry in situ terminal deoxynucleotidyltransferase dUTP nick end-labeling assays same tissues microarray. ELISA α-defensins plasma subjects, patients IPF, IPF-AEx.Measurements Main Results: IPF-AEx samples similar that distinguish lungs. Five hundred seventy-nine differentially expressed (false discovery rate < 5%) between IPF-AEx. these did not indicate any evidence an infectious or overwhelming inflammatory etiology. among most up-regulated genes. α-defensin protein levels also higher localized to epithelium IPF-AEx, where widespread apoptosis detected. α-Defensin increased peripheral blood IPF-AEx.Conclusions: Our results is characterized enhanced epithelial injury proliferation, as reflected increases epithelium. concomitant increase may suggest their use biomarkers this disorder.