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Application of Proteomics in Sarcoidosis.
American Journal of Respiratory Cell and Molecular Biology ( IF 6.4 ) Pub Date : 2020-12-01 , DOI: 10.1165/rcmb.2020-0070ps
Candance R Guerrero 1 , Lisa A Maier 2 , Timothy J Griffin 1 , LeeAnn Higgins 1 , Charles P Najt 1 , David M Perlman 3 , Maneesh Bhargava 3
Affiliation  

Sarcoidosis is a multisystem disease with heterogeneity in manifestations and outcomes. System-level studies leveraging “omics” technologies are expected to define mechanisms contributing to sarcoidosis heterogeneous manifestations and course. With improvements in mass spectrometry (MS) and bioinformatics, it is possible to study protein abundance for a large number of proteins simultaneously. Contemporary fast-scanning MS enables the acquisition of spectral data for deep coverage of the proteins with data-dependent or data-independent acquisition MS modes. Studies leveraging MS-based proteomics in sarcoidosis have characterized BAL fluid (BALF), alveolar macrophages, plasma, and exosomes. These studies identified several differentially expressed proteins, including protocadherin-2 precursor, annexin A2, pulmonary surfactant A2, complement factors C3, vitamin-D–binding protein, cystatin B, and amyloid P, comparing subjects with sarcoidosis with control subjects. Other studies identified ceruloplasmin, complement factors B, C3, and 1, and others with differential abundance in sarcoidosis compared with other interstitial lung diseases. Using quantitative proteomics, most recent studies found differences in PI3K/Akt/mTOR, MAP kinase, pluripotency-associated transcriptional factor, and hypoxia response pathways. Other studies identified increased clathrin-mediated endocytosis and Fcγ receptor–mediated phagocytosis pathways in sarcoidosis alveolar macrophages. Although studies in mixed BAL and blood cells or plasma are limited, some of the changes in lung compartment are detected in the blood cells and plasma. We review proteomics for sarcoidosis with a focus on the existing MS data acquisition strategies, bioinformatics for spectral data analysis to infer protein identity and quantity, unique aspects about biospecimen collection and processing for lung-related proteomics, and proteomics studies conducted to date in sarcoidosis.



中文翻译:

蛋白质组学在结节病中的应用。

结节病是一种多系统疾病,其表现和结果具有异质性。利用“组学”技术的系统级研究有望定义导致结节病异质表现和病程的机制。随着质谱 (MS) 和生物信息学的改进,可以同时研究大量蛋白质的蛋白质丰度。现代快速扫描 MS 能够以数据相关或数据无关的采集 MS 模式采集光谱数据,以深度覆盖蛋白质。在结节病中利用基于 MS 的蛋白质组学的研究已经表征了 BAL 液 (BALF)、肺泡巨噬细胞、血浆和外泌体。这些研究确定了几种差异表达的蛋白质,包括 protocadherin-2 前体、膜联蛋白 A2、肺表面活性剂 A2、补体因子 C3、维生素 D 结合蛋白、胱抑素 B 和淀粉样蛋白 P,将结节病患者与对照组进行比较。其他研究发现,与其他间质性肺病相比,铜蓝蛋白、补体因子 B、C3 和 1 以及其他在结节病中的丰度不同。使用定量蛋白质组学,最近的研究发现 PI3K/Akt/mTOR、MAP 激酶、多能性相关转录因子和缺氧反应途径存在差异。其他研究确定了结节病肺泡巨噬细胞中网格蛋白介导的内吞作用和 Fcγ 受体介导的吞噬作用途径增加。尽管对混合 BAL 和血细胞或血浆的研究有限,但在血细胞和血浆中检测到肺室的一些变化。

更新日期:2020-12-01
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