Variations in expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in nasal mucosa of aspirin-sensitive versus aspirin-tolerant patients with nasal polyposis

Abstract

Background Matrix metalloproteinases (MMPs) are key enzymes responsible for extracellular matrix degradation contributing to the progressive histological changes seen in lower airway disease, including asthma. MMP-9 and TIMP-1 have also shown some role in the pathogenesis of chronic rhinosinusitis (CRS) and nasal polyposis (NP). Objective We aim to determine variability in expression of MMP-9 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), in sinus tissue from distinct patient populations presenting with nasal polyposis. Methods The expression of MMP-9 and TIMP-1 was investigated in nasal polyp tissue from 6 aspirin-sensitive (AS) and 6 aspirin-tolerant (AT) patients undergoing endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis (CRSwNP). Sinus mucosa from 6 patients with chronic rhinosinusitis without nasal polyposis (CRSsNP) was used as control. The MMP-9 and TIMP-1 expression was measured using immunofluorescence technique and graded using manual and computerized methods. Results Expression of TIMP-1 was significantly reduced in the AS group when compared with both the AT and CRSsNP (control) groups (P < .001). The MMP-9/TIMP-1 ratio was significantly increased in the AS group when compared with other patient groups (P < .001). The MMP- 9 expression was similar between study and control groups. Conclusion These results support the importance of MMP-9 and TIMP-1 expression in nasal polyp formation. The decreased expression of TIMP-1 in AS patients may promote the effects of MMP-9 expression and thus contribute to tissue remodeling and inflammatory changes. This finding may lead to further understanding of disease severity and resistance to treatment in this group of patients, as well as the pathogenesis of nasal polyps.

Involvement of the extracellular matrix proteins periostin and tenascin C in nasal polyp remodeling by regulating the expression of MMPs

“…We revealed that fibroblasts and the nasal epithelium are both sources of MMPs within nasal polyps. TIMP‐1 might be able to reduce the effects of the expression of MMP‐9; however, the levels of MMP‐9 and TIMP‐1 were negatively correlated with disease severity in CRS 39,40 . Although higher levels of TIMP‐1 and TIMP‐2 were found in CRSwNPs, we failed to verify the regulatory roles of periostin and tenascin C on TIMPs.…”

“…TIMP‐1 might be able to reduce the effects of the expression of MMP‐9; however, the levels of MMP‐9 and TIMP‐1 were negatively correlated with disease severity in CRS. 39 , 40 Although higher levels of TIMP‐1 and TIMP‐2 were found in CRSwNPs, we failed to verify the regulatory roles of periostin and tenascin C on TIMPs. In this regard, further studies are required to illuminate how TIMPs are induced in nasal polyps.…”

Involvement of the Extracellular Matrix Proteins Periostin and Tenascin C in Nasal Polyp Remodeling by Regulating the Expression of MMPs

“…TIMP-1 might be able to reduce the effects of the expression of MMP-9, however, the levels of MMP-9 and TIMP-1 were negatively correlated with disease severity in CRS. [33,34] Although higher levels of TIMP-1 and TIMP-2 were found in CRSwNPs, we failed to verify the regulatory roles of periostin and tenascin C on TIMPs. In this regard, further studies are required to illuminate how TIMPs are induced in nasal polyps.…”

Downregulation of miR‑29b‑3p promotes α‑tubulin deacetylation by targeting the interaction of matrix metalloproteinase‑9 with integrin β1 in nasal polyps

“…In previous reports, miR-29b-3p was shown to directly and indirectly regulate MMP-2 and MMP-9 expression ( 28 , 29 ). It is commonly known that MMPs are likely to be associated with airway remodeling in CRSwNPs based on the increased expression of MMP-2 and MMP-9 in patients with CRSwNPs compared with control subjects ( 36 - 38 ). Numerous studies have found that the levels of MMPs are significantly increased in CRSwNPs compared with healthy control tissues and that the levels of TIMPs are significantly decreased ( 10 - 13 ).…”

“…Although the cellular mechanisms underlying the development of CRSwNPs remain uncertain, polyp formation occurs due to the protrusion of connective tissue through an initial epithelial defect and remodeling ( 46 ). The present study further demonstrated that MMP-9-integrin β1 complexes promote α-tubulin deacetylation involved in the airway remodeling of CRSwNPs.…”