Expression of matrix metalloproteinases (MMPs) in primary spontaneous pneumothorax: MMP-9 as a potential biomarker for surgical intervention

Abstract

Background: Primary spontaneous pneumothorax (PSP) is usually caused by the spontaneous rupture of pleural blebs or bullae. We aimed to investigate the mechanism of bulla formation related to PSP development. Methods: Twenty-four adolescents with PSP were enrolled prospectively and gene expression analysis of 10 lung tissue biopsies was performed to identify differentially expressed genes associated with PSP. Pathway and network analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) web tool. Results: Gene network analysis revealed pathways related to cell-extracellular matrix interactions were significantly different between lesion and normal sites of lung biopsies. Biologic functions including proteolysis in biological process (BP), extracellular matrix in cellular component (CC), and peptidase, endopeptidase and metallopeptidase activity in molecular function (MF) were predominantly found in up-regulated genes as compared to down-regulated genes. Matrix metalloproteinases (MMPs) genes were overexpressed and MMP-1 and MMP-9 were expressed with more than 10-fold difference. Most importantly, MMP-9 was not only overexpressed in the cells of PSP lung tissues (neutrophils, alveolar macrophage and mesothelial cells) but also was significantly associated with the need for surgical intervention. Conclusions: An imbalance of cell-extracellular matrix interactions caused by MMPs may result in alveolar destruction, distal emphysema and blebs formation, leading to the development of PSP. MMP-9 expression could potentially be a valuable marker for the surgical intervention of adolescent patients with PSP.