Multiplexed Imaging Mass Spectrometry of Histological Staining, N-Glycan and Extracellular Matrix from One Tissue Section: A Tool for Fibrosis Research.
Multiplexed Imaging Mass Spectrometry of Histological Staining, N-Glycan and Extracellular Matrix from One Tissue Section: A Tool for Fibrosis Research.
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DOI：
10.1007/978-1-0716-1593-5_20
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发表时间：
2021-01-01
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影响因子：
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通讯作者：
Angel, Peggi M
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作者：
Clift, Cassandra L;Mehta, Anand;Angel, Peggi M
我们描述了一种多路成像质谱方法，特别适用于纤维化研究。纤维化是一个以细胞外基质（ECM）分泌过多为特征的过程。ECM的积累损害组织和器官功能，促进疾病的进一步发展。将ECM用于纤维化的诊断和治疗是一项持续的分析挑战。最近，我们报道了III型胶原酶在纤维化疾病（包括肝细胞癌、乳腺癌、前列腺癌、肺癌和主动脉瓣狭窄）的薄组织切片中靶向ECM蛋白质组的应用。通过基质辅助激光解吸/电离（MALDI）成像质谱（IMS）检测胶原酶III型肽，可以将ECM肽序列定位到纤维化的特定区域。我们进一步发现，胶原酶III型进入的ECM蛋白质组平均每个蛋白有3.7个位点，这些位点可能是不同的n -糖基化。n -糖基化是ECM蛋白质组的主要翻译后修饰，影响蛋白质的折叠、分泌和组织。了解n -糖基化信号传导和ECM表达调控对纤维化中ECM信号传导有重要意义。
We describe a multiplexed imaging mass spectrometry approach especially suitable for fibrosis research. Fibrosis is a process characterized by excessive extracellular matrix (ECM) secretion. Buildup of ECM impairs tissue and organ function to promote further progression of disease. It is an ongoing analytical challenge to access ECM for diagnosis and therapeutic treatment of fibrosis. Recently, we reported the use of the enzyme collagenase type III to target the ECM proteome in thin histological tissue sections of fibrotic diseases including hepatocellular carcinoma, breast cancer, prostate cancer, lung cancerand aortic valve stenosis. Detection of collagenase type III peptides by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) allows localization of ECM peptide sequences to specific regions of fibrosis. We have further identified that the ECM proteome accessed by collagenase type III has on average 3.7 sites per protein that may be differentially N-glycosylated. N-glycosylation is a major posttranslational modification of the ECM proteome, influencing protein folding, secretion, and organization. Understanding both N-glycosylation signaling and regulation of ECM expression significantly informs on ECM signaling in fibrosis.