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

Abstract

Background: Tissue remodeling caused by increased MMPs is involved in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). We previously found higher levels of periostin and tenascin C in CRSwNPs, but whether they are associated with the dysregulation of MMPs is unknown. Therefore, the present study aimed to investigate the regulatory roles of two ECM proteins in the expression of MMPs in nasal polyps.Methods：The concentrations of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, TIMP-1, TIMP-2, TIMP-3, TIMP-4, periostin, and tenascin C in tissue homogenates of 51 patients with chronic rhinosinusitis with and without nasal polyps and 15 control subjects were measured and their correlations were analyzed. Primary human nasal polyp fibroblasts and epithelial cells were stimulated ex vivo with periostin and tenascin C and the gene expression of MMPs and TIMPs was determined by means of real-time PCR.Results: The protein levels of MMP-3, MMP-7, MMP-8, MMP-9, TIMP-1, TIMP-2, periostin, and tenascin C were significantly higher in patients with CRSwNPs than in healthy control subjects. Periostin was positively correlated with MMP-3 and TIMP-2, and tenascin C was positively correlated with MMP-3, MMP-7, MMP-8, MMP-9 and TIMP-2. Periostin stimulated the gene expression of MMP-3, MMP-7, and MMP-9 in fibroblasts and MMP-7 in epithelial cells ex vivo. Tenascin C stimulated the expression of MMP-3, MMP-8, and MMP-9 in epithelial cells, but not in fibroblasts. The expression of TIMPs in fibroblasts and epithelial cells was affected by neither periostin nor tenascin C. Conclusions：Periostin and tenascin C might be involved in the remodeling of nasal polyps by regulating the expression of different MMPs in epithelial cells and fibroblasts. Our findings have the potential to identify key factors of tissue remodeling in CRSwNPs.

Rhinology in review: from COVID-19 to biologicals

“…More recently, single cell gene expression studies have also revealed distinct populations of epithelial cells and lymphocytes uniquely contributing to CRS pathophysiology (117,118) . Transcriptional changes have largely been validated by proteomic studies (119)(120)(121) as well as cellular and histologic studies of sinonasal mucosa which have highlighted not only importance of inflammatory dysregulation, but tissue remodeling in CRS pathophysiology (122)(123)(124)(125)(126) .…”