Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MA, USA.
Sci Adv. 2021 Jul 23;7(30). doi: 10.1126/sciadv.abf1088. Print 2021 Jul.
Epithelial tissue can transition from a jammed, solid-like, quiescent phase to an unjammed, fluid-like, migratory phase, but the underlying molecular events of the unjamming transition (UJT) remain largely unexplored. Using primary human bronchial epithelial cells (HBECs) and one well-defined trigger of the UJT, compression mimicking the mechanical effects of bronchoconstriction, here, we combine RNA sequencing data with protein-protein interaction networks to provide the first genome-wide analysis of the UJT. Our results show that compression induces an early transcriptional activation of the membrane and actomyosin network and a delayed activation of the extracellular matrix (ECM) and cell-matrix networks. This response is associated with a signaling cascade that promotes actin polymerization and cellular motility through the coordinated interplay of downstream pathways including ERK, JNK, integrin signaling, and energy metabolism. Moreover, in nonasthmatic versus asthmatic HBECs, common genomic patterns associated with ECM remodeling suggest a molecular connection between airway remodeling, bronchoconstriction, and the UJT.
上皮组织可以从一种被堵塞的、固态的、静止的状态转变为一种未被堵塞的、液态的、迁移的状态，但未被堵塞的转变（UJT）的潜在分子事件在很大程度上仍未被探索。在这里，我们使用原代人支气管上皮细胞（HBECs）和 UJT 的一个明确触发因素，即模拟支气管收缩机械效应的压缩，结合 RNA 测序数据和蛋白质-蛋白质相互作用网络，提供了对 UJT 的首次全基因组分析。我们的结果表明，压缩诱导了细胞膜和肌动球蛋白网络的早期转录激活，以及细胞外基质（ECM）和细胞基质网络的延迟激活。这种反应与一个信号级联相关，该级联通过下游途径的协调相互作用，包括 ERK、JNK、整合素信号和能量代谢，促进肌动蛋白聚合和细胞迁移。此外，在非哮喘与哮喘 HBECs 之间，与 ECM 重塑相关的常见基因组模式表明气道重塑、支气管收缩和 UJT 之间存在分子联系。
