Mechanism of matrix metalloproteinases and inhibitors, transforming growth factors β1 on the tissue remodelling in chronic rhinosinusitis
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摘要: 慢性鼻-鼻窦炎(chronic rhinosinusitis, CRS)常以鼻塞、流黏或脓涕、头痛等为主要临床表现,影响日常生活质量,且因其发病机制尚不明确,缺乏准确有效的治疗方法,患者常需进行反复或多种方法联合治疗,这造成了较大的心理负担和经济负担。组织重塑理论是国内外均已认可的慢性鼻-鼻窦炎发病的主要机理,其中细胞外基质(extracellular matrix,ECM)的生成和降解发生失衡是组织重塑的重要特点之一,而CRS不同亚型的组织重塑机理也并不相同,这是由于不同亚型中基质金属蛋白酶(matrix metalloproteinases,MMPs)及其抑制剂(tissue inhibitor of metalloproteinase,TIMPs)表达并不相同。基质金属蛋白酶及其抑制剂除单独影响ECM来参与CRS组织重塑,还通过其摩尔比值来影响ECM代谢以此参与CRS组织重塑。转化生长因子β1(transforming growth factor-β1,TGF-β1)除直接刺激各种通路及细胞因子来影响组织重塑,还可通过TGF-β1/Smad通路来影响ECM代谢,以此参与CRS组织重塑。本文对MMPs、TIMPs、TGF-β1结构及对CRS组织重塑的机制进行综述。Abstract: The main clinical manifestations of chronic rhinosinusitis (CRS) are nasal congestion, mucous or purulent discharge and headache, which affect quality of life. The pathogenesis of CRS is unclear and accurate and effective treatment methods are lacking. Repeated or combined treatments using multiple methods are needed, which impose large psychological and economic burden. Tissue remodelling theory is an important pathogenesis of CRS. The imbalance between the generation and degradation of extracellular matrix (ECM) is one of the important characteristics of tissue remodelling, and the tissue remodelling mechanisms of different subtypes of CRS are different because the expression levels of matrix metalloproteinases (MMPs) and the tissue inhibitor of metalloproteinases (TIMPs) vary by subtype. MMPs and their inhibitors not only affect the ECM but also affect ECM metabolism through molar ratio and participate in CRS tissue remodelling. Transforming growth factor-β1 (TGF-β1) in addition to directly stimulating various pathways and cytokines to affect tissue remodelling, it can also be used TGF-β1/Smad pathway to affect ECM metabolism, so as to participate in CRS tissue remodelling. MMPs, TIMPs and TGF-β1 structure and the mechanism of CRS tissue remodelling are reviewed.
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