Extracellular matrix proteins: A positive feedback loop in lung fibrosis?
Extracellular matrix proteins: A positive feedback loop in lung fibrosis?
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DOI：
10.1016/j.matbio.2013.11.002
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发表时间：
2014-02-01
期刊：
影响因子：
6.9
通讯作者：
Everts, Vincent
中科院分区：
文献类型：
--
作者：
Blaauboer, Marjolein E.;Boeijen, Fee R.;Everts, Vincent
肺纤维化的特点是细胞外基质过度沉积。这不仅影响组织结构和功能，而且还影响成纤维细胞行为，从而影响疾病进展。在这里，我们描述了博莱霉素诱导的肺纤维化发展过程中弹性蛋白、V 型胶原蛋白和生腱蛋白 C 的表达。我们进一步报道了体外实验，阐明了肌成纤维细胞分化对此表达的影响以及细胞外弹性蛋白对肌成纤维细胞分化的影响。通过博来霉素滴注在雌性C57B1/6小鼠中诱导肺纤维化。纤维化诱导后零至五周处死动物。处死前一周合成的胶原蛋白用氘标记。处死后，收集肺组织用于测定新胶原形成、微阵列分析和组织学。人肺成纤维细胞在涂有 I 型胶原或弹性蛋白的组织培养塑料或 BioFlex 培养板上生长，并用 0-10 ng/ml 转化生长因子 (TGF)β(1) 刺激进行肌成纤维细胞分化。通过实时定量PCR分析mRNA表达。博莱霉素诱导的纤维化过程中新胶原的形成与弹性蛋白、V型胶原和生腱蛋白C的基因表达高度相关。在蛋白质水平上，弹性蛋白、V型胶原和生腱蛋白C在肺组织切片中的纤维化区域中高表达。 V型胶原蛋白和生腱蛋白C短暂增加。用 TGF beta(1) 刺激的人肺成纤维细胞强烈增加弹性蛋白、V 型胶原和腱蛋白 C 的基因表达。细胞外弹性蛋白的存在增加了肌成纤维细胞标记物 α 平滑肌肌动蛋白和 I 型胶原的基因表达。在肺纤维化的发展过程中，细胞外基质组成发生巨大变化。弹性蛋白、V 型胶原蛋白和生腱蛋白 C 水平的增加可能是成纤维细胞表达增加的结果；相反，弹性蛋白影响肌成纤维细胞分化。这表明成纤维细胞和细胞外基质成分之间的相互作用可以促进肺纤维化的发展。 (C) 2013 Elsevier B.V. 保留所有权利。
Lung fibrosis is characterized by excessive deposition of extracellular matrix. This not only affects tissue architecture and function, but it also influences fibroblast behavior and thus disease progression. Here we describe the expression of elastin, type V collagen and tenascin C during the development of bleomycin-induced lung fibrosis. We further report in vitro experiments clarifying both the effect of myofibroblast differentiation on this expression and the effect of extracellular elastin on myofibroblast differentiation.Lung fibrosis was induced in female C57B1/6 mice by bleomycin instillation. Animals were sacrificed at zero to five weeks after fibrosis induction. Collagen synthesized during the week prior to sacrifice was labeled with deuterium. After sacrifice, lung tissue was collected for determination of new collagen formation, microarray analysis, and histology. Human lung fibroblasts were grown on tissue culture plastic or BioFlex culture plates coated with type I collagen or elastin, and stimulated to undergo myofibroblast differentiation by 0-10 ng/ml transforming growth factor (TGF)beta(1). mRNA expression was analyzed by quantitative real-time PCR.New collagen formation during bleomycin-induced fibrosis was highly correlated to gene expression of elastin, type V collagen and tenascin C. At the protein level, elastin, type V collagen and tenascin C were highly expressed in fibrotic areas as seen in histological sections of the lung. Type V collagen and tenascin C were transiently increased. Human lung fibroblasts stimulated with TGF beta(1) strongly increased gene expression of elastin, type V collagen and tenascin C. The extracellular presence of elastin increased gene expression of the myofibroblastic markers alpha smooth muscle actin and type I collagen.The extracellular matrix composition changes dramatically during the development of lung fibrosis. The increased levels of elastin, type V collagen and tenascin C are probably the result of increased expression by fibroblastic cells; reversely, elastin influences myofibroblast differentiation. This suggests a reciprocal interaction between fibroblasts and the extracellular matrix composition that could enhance the development of lung fibrosis. (C) 2013 Elsevier B.V. All rights reserved.