Matrix metalloproteinase-7 and matrix metalloproteinase-9 expression is upregulated in congenital lung malformations

Abstract

Background. Congenital lung malformations (CLMs) refer to structural abnormalities of the lungs that occur during fetal development. Matrix metalloproteinases (MMPs) constitute a group of zinc-dependent enzymes, with certain members of this family playing pivotal roles in the remodeling of the lungs both prenatally and postnatally. This study aimed to explore expression levels of MMP-2, MMP-7, and MMP-9 in CLMs which are recognized as pivotal contributors to their clinical pathology. Methods. A total of 41 patients between the ages of 0-17 years that had undergone lung surgery for CLMs between March 2007-July 2023 were analyzed. The demographic features, clinical and pathological findings were recorded. The expression levels of MMP-2, MMP-7 and MMP-9 in patients’ tissues were examined by reverse transcription polymerase chain reaction and compared in CLMs and adjacent normal lung tissues. Results. Among patients with CLMs, 12 patients had congenital pulmonary airway malformations (CPAM, one patient had bilateral lesions), 18 patients had bronchopulmonary sequestration (BPS), 7 patients had congenital lobar overinflation (CLO), and 4 patients had bronchogenic cyst (BC). The higher expression of MMP-7 and MMP-9 in all CLM tissues compared to normal tissue was observed. But, there was a trend in MMP-2 expression in CPAM tissues and MMP-2 showed high expression in the BPS, CLO and BC groups, which was not statistically significant. Upon collective analysis of all groups, it was observed that mRNA expressions of MMP-7 and MMP-9 exhibited greater upregulation in CPAM and BC in comparison to BPS and CLO. Conclusions. Our findings indicate a specific involvement of MMP-7 and MMP-9 in the pathogenesis of CLMs, particularly in CPAM and BC. To the best of our knowledge, this research represents the initial demonstration of MMP expression in CLMs.