Fibroblast to myofibroblast transition is enhanced by increased cell density.
Fibroblast to myofibroblast transition is enhanced by increased cell density.
复制标题
细胞密度增加可促进成纤维细胞向肌成纤维细胞的转变。
DOI：
10.1091/mbc.e20-08-0536
复制
发表时间：
2021-12-01
影响因子：
3.3
通讯作者：
Stroka KM
中科院分区：
文献类型：
--
作者：
Doolin MT;Smith IM;Stroka KM
特发性肺纤维化（IPF）是一种慢性肺部疾病，由猖獗的炎症反应引起过度的细胞外基质（ECM）沉积。IPF患者的肺也发展成纤维母细胞灶，由活化的成纤维细胞和肌成纤维细胞组成。与ECM沉积一致，成纤维细胞病灶内细胞密度的增加对肺成纤维细胞施加了限制力。在这项工作中，我们观察到细胞密度的增加增加了成纤维细胞向肌成纤维细胞转化（FMT）的发生率，但微柱施加的机械限制对FMT的发生率没有影响。我们发现，与中、低密度相比，高密度播种的人肺成纤维细胞在TGF-β1的作用下，表达α-SMA更多，胶原基质沉积更多，这是肌成纤维细胞的特征。这些结果支持了一种假设，即当细胞密集堆积时，hlf更容易响应TGF-β1进行FMT，这种效应可能依赖于OB-cadherin表达的增加。这项工作表明，细胞密度是体外模拟IPF时需要考虑的一个重要因素，这可能表明降低成纤维细胞灶内的细胞密度是减少IPF负担的一种策略。
Idiopathic pulmonary fibrosis (IPF) is a chronic disease of the lung caused by a rampant inflammatory response that results in the deposition of excessive extracellular matrix (ECM). IPF patient lungs also develop fibroblastic foci that consist of activated fibroblasts and myofibroblasts. In concert with ECM deposition, the increased cell density within fibroblastic foci imposes confining forces on lung fibroblasts. In this work, we observed that increased cell density increases the incidence of the fibroblast-to-myofibroblast transition (FMT), but mechanical confinement imposed by micropillars has no effect on FMT incidence. We found that human lung fibroblasts (HLFs) express more α-SMA and deposit more collagen matrix, which are both characteristics of myofibroblasts, in response to TGF-β1 when cells are seeded at a high density compared with a medium or a low density. These results support the hypothesis that HLFs undergo FMT more readily in response to TGF-β1 when cells are densely packed, and this effect could be dependent on increased OB-cadherin expression. This work demonstrates that cell density is an important factor to consider when modelling IPF in vitro, and it may suggest decreasing cell density within fibroblastic foci as a strategy to reduce IPF burden.