Matrix metalloproteinases and their impact on sinusal extension in chronic rhinosinusitis with nasal polyps
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RHINOLOGY
Matrix metalloproteinases and their impact on sinusal extension in chronic rhinosinusitis with nasal polyps Rafael Rossell Malinsky • Fabiana C. P. Valera • Franse´rgio Emı´lio Cavallari Daniel Salgado Ku¨pper • Cristiane Milaneze • Joa˜o S. Silva • Edwin Tamashiro • Wilma T. Anselmo-Lima
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Received: 29 August 2012 / Accepted: 27 September 2012 / Published online: 12 October 2012 Ó Springer-Verlag Berlin Heidelberg 2012
Abstract MMPs (metalloproteinases) and their inhibitor TIMP (tissue inhibitor of metalloproteinases) are important in tissue remodeling and have been implicated in nasal polyp pathophysiology. The objective of the present study was to evaluate gene expression of MMP-1, MMP-2, MMP-9 and TIMP-1 gene expression in nasal polyps and compare them with normal nasal mucosa. Since MMPs could induce a more prominent tissue edema, we also assessed if these gene expressions could be related to a more extensive disease. For the experimental study, 30 nasal polyp samples from patients with CRSwNP (Chronic Rhinosinusitis with Nasal Polyposis) and 19 middle turbinates (MT) from controls were obtained. Gene expression of MMP-1, MMP-2, MMP-9 and TIMP-1 was assessed by qRT-PCR. The expressions of these genes were compared between nasal polyps and controls and correlated to each individual Lund–Mackay score, MMP-1, MMP-2 and MMP-9 were significantly more expressed in nasal polyps than in controls (P \ 0.005, P \ 0.0001 and P \ 0.05 respectively). No expression of TIMP-1 mRNA was detected. There was no correlation between disease extension evaluated by the Lund–Mackay score and MMPs gene expression. The present results demonstrate that there is a significantly higher mRNA gene expression of MMP-1, MMP-2 and MMP-9 in patients with CRSwNP than
R. R. Malinsky F. C. P. Valera F. E. Cavallari D. S. Ku¨pper C. Milaneze J. S. Silva E. Tamashiro W. T. Anselmo-Lima (&) Department of Ophthalmology, Otorhinolaryngology Head and Neck Surgery, Faculty of Medicine of Ribeira˜o Preto, University of Sa˜o Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeira˜o Preto, SP, Brazil e-mail: [email protected]; [email protected]
controls. However, no correlation was observed between MMPs gene expression and sinonasal CT scan extension. Level of Evidence: 2c Keywords Nasal polyps Metalloproteinases MMP TIMP Sinusal mucosa Chronic Rhinosinusitis
Introduction Chronic rhinosinusitis with nasal polyps (CRSwNP) are characterized by prominent edema of the sinonasal mucosa, associated with inflammatory recruitment and local tissue degradation [1]. Some studies have suggested that significant changes in mucosa, such as basement membrane thickening, glandular hyperplasia and edema occur due to an extracellular matrix (ECM) protrusion through an epithelial defect [2]. Degradation of ECM proteins is regulated by matrix-metalloproteinases (MMP), a group of enzymes that collectively degrade most of the ECM components and thus induce persistent tissue trauma [2]. The activity of MMPs is counter balanced by the tiss
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