Physics of bronchial epithelial unjamming

支气管上皮疏通物理学

• 批准号: 10411937
• 负责人: Jeffrey J Fredberg
• 金额: $ 55.74万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10411937
• 关键词: Adherens Junction; Air; Appearance; Back; Behavior; Biological; Biology; Carcinoma; Cell Line; Cells; Cellular biology; Complement; Data; Development; Diffusion; Disease; Duct (organ) structure; E-Cadherin; Electrical Resistance; Embryonic Development; Epithelial; Epithelial Cells; Event; Fingerprint; Foundations; Gatekeeping; Growth; Health; Human; Intervention; Lead; Liquid substance; Literature; Malignant Neoplasms; Maps; Measures; Mechanics; Mesenchymal; Molecular; Morphogenesis; Multicellular Process; N-Cadherin; Neoplasm Metastasis; Organ; PARD6A gene; Permeability; Phenotype; Physics; Physiological; Physiological Processes; Process; Route; Surface; Testing; Tight Junctions; Transitional Epithelium; Vimentin; airway remodeling; airway repair; asthmatic; asthmatic airway; attenuation; body cavity; bronchial epithelium; cell motility; combinatorial; design; epithelial repair; epithelial to mesenchymal transition; fluorescein isothiocyanate dextran; immune function; migration; multiple omics; novel; programs; protein biomarkers; protein protein interaction; slug; transcription factor; wound healing

Abstract A confluent collective of epithelial cells lines every organ surface and body cavity. The epithelial collective typically remains quiescent and non-migratory while performing its routine barrier and immune functions, but becomes dynamic and migratory during embryonic development and airway morphogenesis, during airway repair and asthmatic airway remodeling, as well as during carcinoma invasion and metastasis. In these and other processes, the striking transition between non-migratory versus migratory behaviors is traditionally framed within the context of the epithelial-to-mesenchymal transition (EMT) or the partial EMT (pEMT). During pEMT the epithelial phenotype, which is said to be innately non-migratory, transitions toward a mesenchymal phenotype, which is innately migratory. But to initiate and sustain collective cellular migration, our central hypothesis holds that the EMT/pEMT mechanism as it is canonically defined is not obligatory. Rather, we propose that the newly discovered unjamming transition (UJT) mechanism in many cases elicits collective cellular migration and, importantly, can function independently of the EMT or pEMT. Unjamming is not to be mistaken for cellular migration or for remodeling. But unjamming does create the physical conditions that make cellular migration and remodeling possible. Using the confluent layer of primary human bronchial epithelial cells (HBECs) in air-liquid-interface (ALI) culture, here we propose to: 1) establish the UJT mechanism as an independent route to collective HBEC migration; 2) map in HBECs the molecular interactome of the UJT mechanism; and 3) explain molecular, structural, and migratory features that typify the UJT mechanism. Extensive preliminary data support the tenability of these aims, which are designed to illuminate basic mechanisms that differentiate UJT from EMT.

摘要 一个汇合的上皮细胞集合排列在每个器官表面和体腔。上皮细胞集合体 通常保持静止和非迁移，同时执行其常规屏障和免疫功能，但 在胚胎发育和气道形态发生过程中变得动态和迁移， 修复和哮喘气道重塑，以及在肿瘤浸润和转移过程中。在这些和 在其他过程中，非迁移行为与迁移行为之间的显著转变传统上是 在上皮-间充质转化（EMT）或部分EMT（pEMT）的背景下构建。期间 pEMT上皮表型，据说是天生的非迁移性，向间充质细胞转化， 表型，这是天生的迁移。但是为了启动和维持集体细胞迁移，我们的中枢神经系统 假设认为，EMT/pEMT机制，因为它是规范定义是不是强制性的。而是 我认为，新发现的无干扰跃迁（UJT）机制在许多情况下都是集体的， 细胞迁移，并且重要的是，可以独立于EMT或pEMT发挥作用。解除干扰不是 误认为是细胞迁移或重塑。但解除干扰确实创造了物理条件， 细胞迁移和重塑的可能使用原代人支气管上皮细胞的汇合层 细胞（HBECs）在空气-液体界面（ALI）培养，在这里，我们建议：1）建立UJT机制作为一个 HBEC集体迁移的独立途径; 2）在HBEC中绘制UJT的分子相互作用组 机制;和3）解释分子，结构和迁移的特点，代表UJT机制。 广泛的初步数据支持这些目标的可行性，这些目标旨在阐明基本的 UJT与EMT的区别机制。

项目成果

Airway smooth muscle tone increases actin filamentogenesis and contractile capacity.

气道平滑肌张力增加肌动蛋白丝生成和收缩能力。

• DOI: 10.1152/ajplung.00205.2019
• 发表时间: 2020
• 期刊: American journal of physiology. Lung cellular and molecular physiology
• 作者: Gazzola,Morgan;Henry,Cyndi;Lortie,Katherine;Khadangi,Fatemeh;Park,ChanYoung;Fredberg,JeffreyJ;Bossé,Ynuk
• 通讯作者: Bossé,Ynuk