Microarray detection of gene overexpression in primary spontaneous pneumothorax.
Primary spontaneous pneumothorax (PSP) often occurs after the rupture of small bullae or subpleural blebs in otherwise normal lungs. The underlying mechanism(s) remain unclear. The aim of this study was to identify genes potentially involved in the development of PSP. Microarray analysis was performed to identify specific gene expression patterns. Expression levels of genes identified to be significantly up- or down-regulated in association with PSP were confirmed by real-time polymerase chain reaction (qRT-PCR) and Western blotting. Immunohistochemistry was performed to identify lung cell types highly expressing these genes. Microarray analysis revealed that expression levels of hypoxia-inducible factor-3 alpha (HIF-3alpha) and caspase-8 were significantly up-regulated in tissue from patients with PSP, whereas interferon-gamma, interleukin (IL)-6, and IL-8 were down-regulated (all P < .05). These genes are related to hypoxia, apoptosis, and inflammation. HIF-3alpha and caspase-8 protein levels were increased in samples from patients with PSP. HIF-3alpha and caspase-8 were localized in mesothelial cells, alveolar type II pneumocytes, and bronchoalveolar epithelial cells in samples from patients with PSP. Our findings, although obviously preliminary given the small sample size, suggest that hypoxia, inflammation, and apoptosis may play important roles in the pathogenesis of PSP.
Fang
Hsin-Yuan
HY
Division of Thoracic surgery, Department of Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Lin
Ching-Yuang
CY
Chow
Kuan-Chih
KC
Huang
Hung-Che
HC
Ko
Wen-Je
WJ
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001706:Biopsy; D015153:Blotting, Western; D053181:Caspase 8 / Q000235:genetics; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008168:Lung / Q000737:chemistry* / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011030:Pneumothorax / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013624:Taiwan; D055815:Young Adult
D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D053181:Caspase 8; D007371:Interferon-gamma; D015850:Interleukin-6; D016209:Interleukin-8; D012097:Repressor Proteins; C508606:CXCL8 protein, human; C116973:HIF3A protein, human; C508600:IL6 protein, human; C505530:CASP8 protein, human