Undifferentiated bronchial fibroblasts derived from asthmatic patients display higher elastic modulus than their non-asthmatic counterparts.
Undifferentiated bronchial fibroblasts derived from asthmatic patients display higher elastic modulus than their non-asthmatic counterparts.
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DOI：
10.1371/journal.pone.0116840
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Michalik M
中科院分区：
文献类型：
--
作者：
Sarna M;Wojcik KA;Hermanowicz P;Wnuk D;Burda K;Sanak M;Czyż J;Michalik M
在哮喘发展过程中，上皮细胞和成纤维细胞向收缩表型的分化与支气管壁重塑和气道收缩有关。病理性成纤维细胞向肌成纤维细胞转变（FMT）可由支气管壁局部炎症触发。最近，我们证明，源自哮喘患者的人支气管成纤维细胞（HBF）表现出一些促进其体外 FMT 的固有特征。尽管进行了大量的研究工作，这些特性仍然未知。重要的是，未分化的 HBF 在哮喘过程中的作用被系统地忽略了。具体而言，在体内 FMT 或气道重塑中均未考虑未分化 HBF 的生物力学特性。在这里，我们将原子力光谱与荧光显微镜结合起来，比较来自哮喘患者和非哮喘供体的 HBF 的机械特性和肌动蛋白细胞骨架结构。我们的结果表明，哮喘 HBF 形成厚且对齐的“腹侧”应力纤维，并伴有扩大的粘着斑。哮喘细胞和非哮喘细胞之间细胞骨架结构的差异与哮喘 HBF 的较高弹性模量及其对 TGF-β 诱导的 FMT 的偏好增加相关。由于细胞骨架结构和机械平衡之间的明显联系，我们的观察表明，来自哮喘支气管的 HBF 可以比非哮喘 HBF 产生更高的静态张力。哮喘 HBF 的这一先前未被探索的特性可能对其肌成纤维细胞分化和哮喘发展过程中支气管壁重塑具有潜在重要意义。
During asthma development, differentiation of epithelial cells and fibroblasts towards the contractile phenotype is associated with bronchial wall remodeling and airway constriction. Pathological fibroblast-to-myofibroblast transition (FMT) can be triggered by local inflammation of bronchial walls. Recently, we have demonstrated that human bronchial fibroblasts (HBFs) derived from asthmatic patients display some inherent features which facilitate their FMT in vitro. In spite of intensive research efforts, these properties remain unknown. Importantly, the role of undifferentiated HBFs in the asthmatic process was systematically omitted. Specifically, biomechanical properties of undifferentiated HBFs have not been considered in either FMT or airway remodeling in vivo. Here, we combine atomic force spectroscopy with fluorescence microscopy to compare mechanical properties and actin cytoskeleton architecture of HBFs derived from asthmatic patients and non-asthmatic donors. Our results demonstrate that asthmatic HBFs form thick and aligned ‘ventral’ stress fibers accompanied by enlarged focal adhesions. The differences in cytoskeleton architecture between asthmatic and non-asthmatic cells correlate with higher elastic modulus of asthmatic HBFs and their increased predilection to TGF-β-induced FMT. Due to the obvious links between cytoskeleton architecture and mechanical equilibrium, our observations indicate that HBFs derived from asthmatic bronchi can develop considerably higher static tension than non-asthmatic HBFs. This previously unexplored property of asthmatic HBFs may be potentially important for their myofibroblastic differentiation and bronchial wall remodeling during asthma development.
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影响因子：
7.8
作者：
Gardel, Margaret L.;Sabass, Benedikt;Ji, Lin;Danuser, Gaudenz;Schwarz, Ulrich S.;Waterman, Clare M.
通讯作者：
Waterman, Clare M.
影响因子：
4
作者：
Provenzano, Paolo P.;Keely, Patricia J.
通讯作者：
Keely, Patricia J.
影响因子：
--
作者：
Chen, Jianxin;Li, Hongxia;Wang, James H. -C.
通讯作者：
Wang, James H. -C.
影响因子：
1.6
作者：
HUTTER, JL;BECHHOEFER, J
通讯作者：
BECHHOEFER, J
影响因子：
14.2
作者：
Al-Muhsen, Saleh;Johnson, Jill R.;Hamid, Qutayba
通讯作者：
Hamid, Qutayba