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 these 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 were analyzed by adjusted logistic regression and spearman correlation test. 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. The adjusted logistic regression analyses showed that MMP‐3, MMP‐7, MMP‐8, MMP‐9, TIMP‐2, periostin, and tenascin C were related to the occurrence of CRSwNP. Spearman correlation test showed 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, MMP‐8, and MMP‐9 in fibroblasts and MMP‐9 in epithelial cells ex vivo. Tenascin C stimulated the expression of MMP‐3, MMP‐7, MMP‐8, and MMP‐9 in epithelial cells. 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.

Periostin as a biomarker in chronic rhinosinusitis: A contemporary systematic review

“…A high degree of heterogeneity was noted regarding the tissue samples anatomical origin for both patients and controls. More specifically, 15 papers 19,23–26,29–37,52 studied CRSwNP polyp tissue; among them some also analyzed mucosal samples from the inferior turbinate, 29,31 the middle turbinate, 24 or mucus samples 36 …”

“…A high degree of heterogeneity was noted regarding the tissue samples anatomical origin for both patients and controls. More specifically, 15 papers 19,[23][24][25][26][29][30][31][32][33][34][35][36][37]52 studied CRSwNP polyp tissue; among them some also analyzed mucosal samples from the inferior turbinate, 29,31 the middle turbinate, 24 or mucus samples. 36 Out of the 15 aforementioned studies six compared CRSwNP samples to both CRSsNP and controls; CRSsNP samples were derived from ethmoid sinus, 19,26,37 anterior nasal cavity, 19 middle turbinate, 24 "diseased sinuses," 23 or "sinonasal tissue."…”

“…More specifically, 15 papers 19,[23][24][25][26][29][30][31][32][33][34][35][36][37]52 studied CRSwNP polyp tissue; among them some also analyzed mucosal samples from the inferior turbinate, 29,31 the middle turbinate, 24 or mucus samples. 36 Out of the 15 aforementioned studies six compared CRSwNP samples to both CRSsNP and controls; CRSsNP samples were derived from ethmoid sinus, 19,26,37 anterior nasal cavity, 19 middle turbinate, 24 "diseased sinuses," 23 or "sinonasal tissue." 33 Control samples were obtained from inferior turbinate, 19,26,37 ethmoid sinus, 19 middle turbinate, 24 sphenoid sinus, 23 or uncinate process.…”

Circulating MMP-12 as Potential Biomarker in Evaluating Disease Severity and Efficacy of Sublingual Immunotherapy in Allergic Rhinitis

“…Similarly, MMP12, a proinflammatory factor mainly produced by macrophages, is demonstrated to be involved in the development of allergic diseases [ 14 , 29 ]. Prior publications found that abnormal MMP expressions were implicated in various chronic inflammatory disorders, including asthma [ 30 ], chronic rhinosinusitis with nasal polyp [ 31 ], and inflammatory bowel disease [ 32 ]. Recent studies found that MMP12 was mainly secreted by M2-type macrophages, and the enhanced MMP-12 levels were proved to promote Th2-type inflammatory response and aggravated allergic airway inflammation in airway inflammatory diseases [ 14 , 33 ].…”

Immunological Aspects of Chronic Rhinosinusitis

“…In addition, several multifunctional proteins are upregulated in the mucus of CRSwNP such as cystatin 2, pappalysin-A, periostin, and serpins. Periostin expression is associated with the presence of basement membrane thickening (BMT), fibrosis, and tissue eosinophilia [ 9 ] and may be involved in the remodeling of NPs [ 10 ]. Cystatin 2 triggers epithelial barrier functions and immunomodulation.…”