Decreased Laminin Expression by Human Lung Epithelial Cells and Fibroblasts Cultured in Acellular Lung Scaffolds from Aged Mice.
Decreased Laminin Expression by Human Lung Epithelial Cells and Fibroblasts Cultured in Acellular Lung Scaffolds from Aged Mice.
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DOI：
10.1371/journal.pone.0150966
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Panoskaltsis-Mortari A
中科院分区：
文献类型：
--
作者：
Godin LM;Sandri BJ;Wagner DE;Meyer CM;Price AP;Akinnola I;Weiss DJ;Panoskaltsis-Mortari A
随着年龄的增长，肺在功能和结构上都发生了变化。然而，年龄对细胞外基质（ECM）的相关影响以及对肺细胞行为的相应影响尚不清楚。我们假设年老动物的ECM会在健康接种细胞中诱导衰老相关的表型变化。去细胞化的全器官支架为检查ECM信号如何影响细胞表型提供了一个强大的模型。年龄对原生和去细胞化小鼠肺中ECM组成的影响，以及年轻和年老的脱细胞ECM对人支气管上皮细胞（hBECs）和肺成纤维细胞（hLFs）的影响。与幼龄（3周）肺相比，原生年龄（1岁）肺的层粘连蛋白α3和α4、弹性蛋白和纤维连接蛋白表达降低，胶原蛋白表达升高。脱细胞肺外膜的蛋白质组学分析也显示了类似的结果，与年轻肺外膜相比，脱细胞老年肺外膜的结构蛋白多样性较低。在老年ECM中，与年轻ECM相比，hBECs和hLFs分别表现出较低的层粘连蛋白α3和α4基因表达，与老年ECM的层粘连蛋白缺乏相似。ECM的改变似乎是增强衰老相关表型的重要因素，并可能为衰老相关肺部疾病的机制提供线索。
The lung changes functionally and structurally with aging. However, age-related effects on the extracellular matrix (ECM) and corresponding effects on lung cell behavior are not well understood. We hypothesized that ECM from aged animals would induce aging-related phenotypic changes in healthy inoculated cells. Decellularized whole organ scaffolds provide a powerful model for examining how ECM cues affect cell phenotype. The effects of age on ECM composition in both native and decellularized mouse lungs were assessed as was the effect of young vs old acellular ECM on human bronchial epithelial cells (hBECs) and lung fibroblasts (hLFs). Native aged (1 year) lungs demonstrated decreased expression of laminins α3 and α4, elastin and fibronectin, and elevated collagen, compared to young (3 week) lungs. Proteomic analyses of decellularized ECM demonstrated similar findings, and decellularized aged lung ECM contained less diversity in structural proteins compared to young ECM. When seeded in old ECM, hBECs and hLFs demonstrated lower gene expression of laminins α3 and α4, respectively, as compared to young ECM, paralleling the laminin deficiency of aged ECM. ECM changes appear to be important factors in potentiating aging-related phenotypes and may provide clues to mechanisms that allow for aging-related lung diseases.