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천식에서 Matrix Metalloproteinase-9의 역할

Role of Matrix Metalloproteinase-9 in Asthma

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참고문헌

주제분류소아과학

초록

알레르기 염증과 기도 개형은 천식의 병리로서 기도의 구조적 변형에 MMPs가 주요한 역할을 하고 있다. MMPs가 중성구, 호산구와 대식세포 같은 염증세포의 이동과 기능에 영향을 미치고, 세포외기질의 침착과 분해에 영향을 미쳐서 천식 기관지의 구조적 변화에 중요한 역할을 하고 있다. TIMPs는 MMPs와 분자량으로 1 : 1의 비로 결합을 하는데, MMPs/TIMPs의 비가 올라가면 조직 손상이 올 수 있고, 반대로 떨어지면 조직에 섬유화가 증가한다. MMP-9은 MMPs 중에서 천식에서 중요한 역할을 하고 있으며, 급성 천식 환자에서와 알레르겐으로 유발한 천식 환자의 기관지폐포 세척액에서 MMP-9이 증가하였고, 다시 급성 천식이 가라앉은 후에는 MMP-9이 정상으로 돌아왔다. 뿐 아니라, 스테로이드로 치료한 후에도 MMP-9의 수치가 감소하고, TIMPs는 증가하였다. 천식의 알레르기 염증이 있는 기관지에서 MMP-9이 증가하고, MMPs의 억제제를 사용하면 알레르기 염증이 감소하는 것은 확실한 것 같지만, MMP-9 결핍 쥐를 이용한 연구에서는 서로 상이한 결과가 보고되기도 하였다. 그래서 천식 치료제로서의 MMP-9 억제제의 역할에 대해서는 좀 더 많은 연구가 필요할 것으로 사료된다.

Abstract

Variable airway obstruction, increased bronchial hyperresponsiveness, allergic inflammatory reaction and airway remodeling are main characteristics of asthma. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases(TIMPs) do play important roles to pathogenesis and pathology of asthma via influence on the function and migration of inflammatory cells as well as extracellular matrix(ECM) deposition and degradation. MMP-9 is the predominant MMP in asthma and chronic obstructive pulmonary disease(COPD), and its expression is enhanced when asthma patients have spontaneous exacerbations or in response to local instillation of allergen in the airway. As acute inflammation of asthma resolves, MMP-9 levels return to normal. TIMPs bind MMPs in a 1 : 1 fashion. Thus, an increase in the molar ratio of MMP/TIMP can favor tissue injury, while the reverse ratio could be associated with increased fibrosis. Glucocorticosteroids could downregulate MMPs and enhance TIMPs. Even though it is clear that stimulated allergic inflammation in airway is associated with increased expression of MMPs, whether specific inhibitors of MMPs could reduce airway structural changes and facilitate orderly healing in asthma is still unknown.

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관련 논문AI추천

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