当前位置： SCI文献检索 > AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE期刊下所有文献 > Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis.

Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis.

Abstract：

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

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Konishi K,Gibson KF,Lindell KO,Richards TJ,Zhang Y,Dhir R,Bisceglia M,Gilbert S,Yousem SA,Song JW,Kim DS,Kaminski N

doi

10.1164/rccm.200810-1596OC

subject

Has Abstract

pub_date

2009-07-15 00:00:00

pages

167-75

issue

eissn

1073-449X

issn

1535-4970

pii

200810-1596OC

journal_volume

180

pub_type

杂志文章

在线工具

Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis.