Localization and potential role of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 and-2 in different phases of bronchopulmonary dysplasia
Localization and potential role of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 and-2 in different phases of bronchopulmonary dysplasia
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DOI：
10.1203/00006450-200112000-00022
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发表时间：
2001-12-01
影响因子：
3.6
通讯作者：
Versnel, MA
中科院分区：
文献类型：
--
作者：
Dik, WA;De Krijger, RR;Versnel, MA
支气管肺发育不良（BPD）可在因透明膜病（HMD）需要机械通气的早产儿中发展。BPD的发展可分为急性期、再生期、过渡期和慢性期。在这些不同的阶段，肺实质的广泛重塑，肺泡的再上皮化和纤维化的形成。基质金属蛋白酶-1 （MMP-1）是一种参与再上皮化过程的酶，MMP-1活性的失调有助于纤维化。研究了肺组织中MMP-1及其抑制剂组织金属蛋白酶抑制剂(TIMP)- 1和TIMP-2在BPD不同发展阶段死亡婴儿肺组织中的定位。在所有研究病例（n = 50）中，ii型肺细胞对MMP-1、TEMP-1和TIMP-2具有免疫反应性。在BPD的急性和再生期，ii型肺细胞使损伤的肺泡重新上皮化。这可能表明由ii型肺细胞表达的MMP-1及其抑制剂在急性肺损伤后的再上皮化过程中发挥作用。尽管在BPD发展过程中，ii型肺细胞的MMP-1染色强度保持不变，但TIMP-1在慢性纤维化期增加。与MMP-1相比，TIMP-1的相对升高表明慢性BPD中h型肺细胞的胶原溶解活性降低，并可能导致纤维化。慢性BPD的纤维化灶含有对MMP- 1、TIMP-和-2有免疫反应的成纤维细胞。这可能表明成纤维细胞胶原转换的减少有助于BPD发展中的纤维化。
Bronchopulmonary dysplasia (BPD) can evolve in prematurely born infants who require mechanical ventilation because of hyaline membrane disease (HMD). The development of BPD can be divided in an acute, a regenerative, a transitional and a chronic phase. During these different phases, extensive remodeling of the lung parenchyma with re-epithelialization of the alveoli and formation of fibrosis occurs. Matrix metalloproteinase-1 (MMP-1) is an enzyme that is involved in re-epithelialization processes, and dysregulation of MMP-1 activity contributes to fibrosis. Localization of MMP-1 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)- 1 and TIMP-2, were investigated in lung tissue obtained from infants who died during different phases of BPD development. In all studied cases (n = 50) type-II pneumocytes were found to be immunoreactive for MMP-1, TEMP-1, and TIMP-2. During the acute and regenerative phase of BPD, type-II pneumocytes re-epithelialize the injured alveoli. This may suggest that MMP-1 and its inhibitors, expressed by type-II pneumocytes, play a role in the reepithelialization process after acute lung injury. Although MMP-1 staining intensity remained constant in type-II pneumocytes during BPD development, TIMP-1 increased during the chronic fibrotic phase. This relative elevation of TIMP-1 compared with MMP-1 is indicative for reduced collagenolytic activity by type-H pneumocytes in chronic BPD and may contribute to fibrosis. Fibrotic foci in chronic BPD contained fibroblasts immunoreactive for MMP- I and TIMP- and -2. This may indicate that decreased collagen turnover by fibroblasts contributes to fibrosis in BPD development.