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.
基金:
National Key R&D Program of China [2016YFC0905200]; Program for the Changjiang Scholars and Innovative Research TeamProgram for Changjiang Scholars & Innovative Research Team in University (PCSIRT) [IRT13082]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81630023, 81570893, 81970852]; Beijing Municipal Science and Technology Project [Z181100001618002]; Beijing Bai-Qian-Wan talent Project [2019A32]; Public Welfare Development and Reform Pilot Project [2019-10]; CAMS Innovation Fund for Medical Sciences [2019-I2M-5-022]
第一作者机构:[1]Capital Med Univ, Beijing Tongren Hosp, Dept Otorhinolaryngol Head & Neck Surg, Beijing, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Capital Med Univ, Beijing Tongren Hosp, Dept Otorhinolaryngol Head & Neck Surg, Beijing, Peoples R China[2]Beijing Inst Otorhinolaryngol, Beijing Key Lab Nasal Dis, Beijing, Peoples R China[*1]Capital Med Univ, Beijing Tongren Hosp, Beijing Inst Otorhinolaryngol, Dept Otorhinolaryngol Head & Neck Surg, 17 Hougouhutong, Beijing 100005, Peoples R China
推荐引用方式(GB/T 7714):
Du Kun,Wang Min,Zhang Nan,et al.Involvement of the extracellular matrix proteins periostin and tenascin C in nasal polyp remodeling by regulating the expression of MMPs[J].CLINICAL AND TRANSLATIONAL ALLERGY.2021,11(7):doi:10.1002/clt2.12059.
APA:
Du, Kun,Wang, Min,Zhang, Nan,Yu, Pei,Wang, Ping...&Bachert, Claus.(2021).Involvement of the extracellular matrix proteins periostin and tenascin C in nasal polyp remodeling by regulating the expression of MMPs.CLINICAL AND TRANSLATIONAL ALLERGY,11,(7)
MLA:
Du, Kun,et al."Involvement of the extracellular matrix proteins periostin and tenascin C in nasal polyp remodeling by regulating the expression of MMPs".CLINICAL AND TRANSLATIONAL ALLERGY 11..7(2021)