分拣细胞蛋白质组学揭示了at1相关的上皮角化表型,并提示人支气管肺发育不良中内皮氧化还原失衡。

IF 3.5 2区 医学 Q1 PHYSIOLOGY
Mereena George Ushakumary, William B Chrisler, Gautam Bandyopadhyay, Heidie L Huyck, Brittney L Gorman, Naina Almazbekovna Beishembieva, Ariana Pitonzo, Zhenli J Lai, Thomas L Fillmore, Isaac Kwame Attah, Gail Deutsch, Jeffrey M Purkerson, Andrew M Dylag, Ravi S Misra, James P Carson, Joshua N Adkins, Gloria Pryhuber, Geremy C Clair
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引用次数: 0

摘要

支气管肺发育不良(BPD)是一种以炎症和瘢痕形成为特征的新生儿肺部疾病,可导致长期组织损伤。以前的全组织蛋白质组学鉴定了bpd特异性蛋白质组的变化和细胞类型的转变。人们对疾病中特定细胞群的蛋白质组水平变化知之甚少。在这里,我们根据正常和BPD人肺上皮细胞(EPI)和内皮细胞(ENDO)的不同表面标记对它们进行了分类。采用低输入兼容样品制备方法(MicroPOT),提取蛋白质并消化成肽,进行液相色谱-串联质谱(LC-MS/MS)蛋白质组学分析。在检测到的4970个蛋白中,293个蛋白在EPI群体中被大量调节,422个蛋白在ENDO细胞中被调节。在BPD EPIs中观察到与肌动蛋白-细胞骨架功能相关的蛋白(如SCEL、LMO7和TBA1B)的调节。通过共聚焦成像和分析,我们证实了在人BPD肺中存在异常的多层样结构,包括SCEL和LMO7,已知与表皮角化有关。这是首个关于BPD中聚酰基化相关蛋白积累的报道。它们在肺泡实质中的定位,主要与肺泡1型(AT1)细胞有关,表明在BPD损伤后反应中起作用。在ENDOs中,氧化还原平衡和线粒体功能通路被调节。在这两个群体中,可选择的mRNA剪接和细胞增殖功能均升高,表明细胞祖细胞命运可能失调。本研究首次表征了BPD肺上皮细胞和内皮细胞的蛋白质组,确定了BPD发病机制的人群特异性变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sorted-Cell Proteomics Reveals an AT1-Associated Epithelial Cornification Phenotype and Suggests Endothelial Redox Imbalance in Human Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a neonatal lung disease characterized by inflammation and scarring leading to long-term tissue damage. Previous whole tissue proteomics identified BPD-specific proteome changes and cell type shifts. Little is known about the proteome-level changes within specific cell populations in disease. Here, we sorted epithelial (EPI) and endothelial (ENDO) cell populations based on their differential surface markers from normal and BPD human lungs. Using a low-input compatible sample preparation method (MicroPOT), proteins were extracted and digested into peptides and subjected to Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) proteome analysis. Of the 4,970 proteins detected, 293 were modulated in abundance or detection in the EPI population and 422 were modulated in ENDO cells. Modulation of proteins associated with actin-cytoskeletal function such as SCEL, LMO7, and TBA1B were observed in the BPD EPIs. Using confocal imaging and analysis, we validated the presence of aberrant multilayer-like structures comprising SCEL and LMO7, known to be associated with epidermal cornification, in the human BPD lung. This is the first report of accumulation of cornification-associated proteins in BPD. Their localization in the alveolar parenchyma, primarily associated with alveolar type 1 (AT1) cells, suggests a role in the BPD post-injury response. In the ENDOs, redox balance and mitochondrial function pathways were modulated. Alternative mRNA splicing and cell proliferative functions were elevated in both populations suggesting potential dysregulation of cell progenitor fate. This study characterized the proteome of epithelial and endothelial cells from the BPD lung for the first time, identifying population-specific changes in BPD pathogenesis.

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来源期刊
CiteScore
9.20
自引率
4.10%
发文量
146
审稿时长
2 months
期刊介绍: The American Journal of Physiology-Lung Cellular and Molecular Physiology publishes original research covering the broad scope of molecular, cellular, and integrative aspects of normal and abnormal function of cells and components of the respiratory system. Areas of interest include conducting airways, pulmonary circulation, lung endothelial and epithelial cells, the pleura, neuroendocrine and immunologic cells in the lung, neural cells involved in control of breathing, and cells of the diaphragm and thoracic muscles. The processes to be covered in the Journal include gas-exchange, metabolic control at the cellular level, intracellular signaling, gene expression, genomics, macromolecules and their turnover, cell-cell and cell-matrix interactions, cell motility, secretory mechanisms, membrane function, surfactant, matrix components, mucus and lining materials, lung defenses, macrophage function, transport of salt, water and protein, development and differentiation of the respiratory system, and response to the environment.
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