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

Kun Du; Min Wang; Nan Zhang; Pei Yu; Ping Wang; Ying Li; Xiangdong Wang; Luo Zhang; Claus Bachert

doi:10.1002/clt2.12059

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

Clin Transl Allergy. 2021 Sep 6;11(7):e12059. doi: 10.1002/clt2.12059. eCollection 2021 Aug.

Authors

Kun Du¹, Min Wang^{1

2}, Nan Zhang³, Pei Yu¹, Ping Wang^{1

2}, Ying Li^{1

2}, Xiangdong Wang^{1

2}, Luo Zhang^{1

2}, Claus Bachert^{3

4}

Affiliations

¹ Department of Otorhinolaryngology Head and Neck Surgery Beijing Tongren Hospital Capital Medical University Beijing China.
² Beijing Key laboratory of Nasal Diseases Beijing Institute of Otorhinolaryngology Beijing China.
³ Department of Oto-Rhino-Laryngology Upper Airways Research Laboratory Ghent University Hospital Ghent Belgium.
⁴ Department of Clinical Sciences, Intervention and Technology Division of ENT Diseases Karolinska Institute Stockholm Sweden.

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.

Keywords: Gewebeumbau; Hemmer der Gewebe‐Metalloproteinase; MMPs; Matrix Metalloproteinase; Nasenpolyp; Periostal Protein; TIMPs; Tenascin; nasal polyps; periostin; remodeling; tenascin C.