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首页> 外文期刊>Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG >Membrane type-matrix metalloproteinases in idiopathic pulmonary fibrosis.
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Membrane type-matrix metalloproteinases in idiopathic pulmonary fibrosis.

机译：特发性肺纤维化中的膜型基质金属蛋白酶。

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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by fibroblast expansion and extracellular matrix accumulation. Some secreted matrix metalloproteinases (MMPs) as MMP2 are highly upregulated in IPF lungs. Membrane-type (MT)-MMPs participate in the activation of pro-MMP2. However, they have not been examined in IPF. METHODS: Type I transmembrane MT-MMPs, MT1, MT2, MT3, and MT5-MMP were analyzed by real-time PCR and immunohistochemistry in IPF and normal lungs. MMP-2 was also immunolocalized and evaluated by gelatin zymography in BAL fluids. Additionally, the MT-MMPs were examined by real time PCR in lung fibroblasts stimulated with TGF-beta1 and IFN-gamma. RESULTS: MT1-MMP, was the most highly expressed followed by MT2- and MT5-MMP, and by a moderate expression of MT3-MMP. Regarding their localization, MT1- and MT2-MMPs were found in alveolar epithelial cells, MT3-MMP in fibroblasts from fibroblastic foci and alveolar epithelial cells and MT5-MMP in basal bronchiolar epithelial cells and in areas of squamous metaplasia. MMP2 was localized in alveolar and basal bronchiolar epithelial cells and fibroblasts, and increased active enzyme was observed in BAL fluids. In lung fibroblasts, TGF-beta1 induced a strong upregulation of MT3-MMP, both at the gene and protein level. This effect was blocked by genistein, a protein tyrosin kinase inhibitor and partially repressed by SB203580 a p38 MAP kinase inhibitor. IFN-gamma had no effect. CONCLUSIONS: MT-MMPs are expressed in IPF, in the same cell types as MMP2. Mostly by different types of epithelial cells a pivotal component in the aberrant remodeling of the lung microenvironment. Interestingly MT3-MMP that was found in fibroblastic foci was upregulated in vitro by TGF-beta1 a potent profibrotic mediator.
机译：背景：特发性肺纤维化（IPF）的特征是成纤维细胞扩张和细胞外基质积聚。 IPF肺中某些分泌的基质金属蛋白酶（MMPs）（如MMP2）高度上调。膜型（MT）-MMP参与pro-MMP2的激活。但是，它们尚未在IPF中进行检查。方法：采用实时荧光定量PCR和免疫组化技术在IPF和正常肺中分析I型跨膜MT-MMP，MT1，MT2，MT3和MT5-MMP。 MMP-2也进行了免疫定位，并通过明胶酶谱法在BAL液中进行了评估。此外，MT-MMPs通过实时PCR检测TGF-beta1和IFN-γ刺激的肺成纤维细胞中。结果：MT1-MMP表达最高，其次是MT2-和MT5-MMP，中等表达是MT3-MMP。关于它们的定位，在肺泡上皮细胞中发现了MT1-和MT2-MMP，在成纤维细胞灶和肺泡上皮细胞的成纤维细胞中发现了MT3-MMP，在基底细支气管上皮细胞和鳞状化生区域中发现了MT5-MMP。 MMP2定位在肺泡和基底细支气管上皮细胞和成纤维细胞中，并且在BAL液中观察到活性酶增加。在肺成纤维细胞中，TGF-beta1在基因和蛋白质水平上都诱导MT3-MMP的强烈上调。这种作用被染料木黄酮（一种蛋白酪氨酸激酶抑制剂）阻断，被SB203580（一种p38 MAP激酶抑制剂）部分抑制。 IFN-γ没有作用。结论：MT-MMP在IPF中表达，与MMP2具有相同的细胞类型。主要由不同类型的上皮细胞引起，在肺微环境异常重塑中起关键作用。有趣的是，在成纤维细胞灶中发现的MT3-MMP在体外由有效的纤维化介质TGF-beta1上调。

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