Lung Biology, Department Experimental Medical Science, Lund University, Lund, Sweden.
Division of Infection Medicine, Department Clinical Sciences, Lund University, Lund, Sweden.
Sci Rep. 2018 Apr 3;8(1):5409. doi: 10.1038/s41598-018-23702-x.
Remodelling of the extracellular matrix is accomplished by altering the balance between matrix macromolecule production and degradation. However, it is not well understood how cells balance production of new matrix molecules and degradation of existing ones during tissue remodelling and regeneration. In this study, we used decellularized lung scaffolds repopulated with allogenic lung fibroblasts cultured with stable isotope labelled amino acids to quantify the balance between matrix production and degradation at a proteome-wide scale. Specific temporal dynamics of different matrisome proteins were found to correspond to the proliferative activity of the repopulating cells and the degree of extracellular deposition. The remodeling of the scaffold was characterized by an initial phase with cell proliferation and high production of cell adhesion proteins such as emilin-1 and fibronectin. Extended culture time resulted in increased levels of core matrisome proteins. In a comparison with monolayer cultures on plastic, culture in lung scaffolds lead to a pronounced accumulation of proteoglycans, such as versican and decorin, resulting in regeneration of an extracellular matrix with greater resemblance to native lung tissue compared to standard monolayer cultures. Collectively, the study presents a promising technique for increasing the understanding of cell- extracellular matrix interactions under healthy and diseased conditions.
细胞外基质的重塑是通过改变基质大分子的产生和降解之间的平衡来实现的。然而，细胞在组织重塑和再生过程中如何平衡新基质分子的产生和现有基质分子的降解还不是很清楚。在这项研究中，我们使用同种异体肺成纤维细胞重构成的去细胞化肺支架，并使用稳定同位素标记的氨基酸进行培养，以在蛋白质组范围内定量测量基质产生和降解之间的平衡。不同基质蛋白的特定时间动态与再生细胞的增殖活性和细胞外沉积程度相对应。支架的重塑以细胞增殖和细胞黏附蛋白（如弹力蛋白 1 和纤维连接蛋白）高产生的初始阶段为特征。延长培养时间会导致核心基质蛋白水平升高。与在塑料上的单层培养相比，在肺支架中的培养导致糖胺聚糖（如 versican 和 decorin）的显著积累，从而再生出与标准单层培养相比更类似于天然肺组织的细胞外基质。总的来说，该研究为在健康和患病条件下增加对细胞-细胞外基质相互作用的理解提供了一种有前途的技术。
