风湿

特发性肺纤维化肺泡上皮细胞MMP28的表达及定位

作者:Maldonado M, et al. 翻译:北医三院 麻贞贞 来源:中国风湿病公众论坛 日期:2018-05-22
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         特发性肺纤维化肺泡上皮细胞MMP28的表达及定位

关键字:  特发性肺纤维化 

        摘要:特发性肺纤维化(IPF)是一种病因不明的与年龄相关的慢性进行性疾病。越来越多的证据表明,异常活化的肺泡上皮细胞诱导成纤维细胞群的增殖与活化,导致肺结构的破坏。

        在IPF中,一些基质金属蛋白酶(MMPs)表达上调,表明它们在IPF的发病或进展中可能扮演重要角色。我们研究了MMP28在这一疾病中的表达,并评价其在两种肺泡上皮细胞系和人原代支气管上皮细胞中的功能效应,我们发现,在两组不同的IPF患者中,该酶在支气管(尖端和细胞质定位)和肺泡上皮细胞(细胞质和核定位)中均有表达。在体外实验中,MMP28基因沉默可减缓上皮细胞的增殖和延迟伤口闭合,而过表达显示出相反的效果,其可使细胞免受凋亡并增强上皮间质转化(EMT)过程。我们的研究结果表明,MMP28在IPF肺上皮细胞中呈高表达,其以促进增殖和表型转换的催化依赖性的方式参与IPF的发生发展。

        Abstract

        Idiopathic Pulmonary Fibrosis (IPF) is a chronicand progressive aging-associated disease of unknown etiology. Growing body ofevidence indicates that aberrant activated alveolar epithelial cells induce theexpansion and activation of the fibroblast population leading to thedestruction of the lung architecture. Some Matrix Metalloproteinases (MMPs) areupregulated in IPF, indicating that they may be important in the pathogenesisand/or progression of IPF. Here, we studied the expression of MMP28 in thisdisease and evaluated its functional effects in two alveolar epithelial celllines and in human primary bronchial epithelial cells. We found that the enzymeis expressed in bronchial (apical and cytoplasmic localization) and alveolarepithelial cells (cytoplasmic and nuclear localization) in two different IPFgroups of patients. In vitro, MMP28 epithelial silencing decreased theproliferation rate and delayed wound closing, while overexpression showed theopposite effects, protected from apoptosis and enhanced epithelial-mesenchymaltransition (EMT). Our findings demonstrate that MMP28 is upregulated inepithelial cells from IPF lungs where it may play a role in increasing theproliferative and migratory phenotype in a catalytic-dependent manner.

        引自:Maldonado M, Salgadoaguayo A, Herrera I, et al. Upregulation andNuclear Location of MMP28 in Alveolar Epithelium of Idiopathic PulmonaryFibrosis.[J]. American Journal of Respiratory Cell & Molecular Biology,2018.

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