Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.
Departamento de Bioquimica y Biologia Molecular, Universidad de Oviedo, Oviedo, Spain.
Biochim Biophys Acta Mol Cell Res. 2017 Nov;1864(11 Pt B):2210-2219. doi: 10.1016/j.bbamcr.2017.08.004. Epub 2017 Aug 7.
The protease degradome is defined as the complete repertoire of proteases and inhibitors, and their nonfunctional homologs present in a cell, tissue or organism at any given time. We review the tissue distribution of virtually the entire degradome in 23 different human tissues and 6 ovarian cancer cell lines. To do so, we developed the CLIP-CHIP™, a custom microarray based on a 70-mer oligonucleotide platform, to specifically profile the transcripts of the entire repertoire of 473 active human proteases, 156 protease inhibitors and 92 non-proteolytically active homologs known at the design date using one specific 70-mer oligonucleotide per transcript. Using the CLIP-CHIP™ we mapped the expression profile of proteases and their inhibitors in 23 different human tissues and 6 ovarian cancer cell lines in 104 sample datasets. Hierarchical cluster analysis showed that expression profiles clustered according to their anatomic locations, cellular composition, physiologic functions, and the germ layer from which they are derived. The human ovarian cancer cell lines cluster according to malignant grade. 110 proteases and 42 inhibitors were tissue specific (1 to 3 tissues). Of these 110 proteases 69% (74) are mainly extracellular, 30% (34) intracellular and 1% intramembrane. Notably, 35% (197/565) of human proteases and 30% (47/156) of inhibitors were ubiquitously expressed in all 23 tissues; 27% (155) of proteases and 21% (32) of inhibitors were broadly expressed in 4-20 tissues. Our datasets provide a valuable resource for the community of baseline protease and inhibitor relative expression in normal human tissues and can be used for comparison with diseased tissue, e.g. ovarian cancer, to decipher pathogenesis, and to aid drug development. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.
蛋白酶降解组被定义为在特定时间内存在于细胞、组织或生物体中的完整蛋白酶和抑制剂 repertoire，以及它们的非功能同源物。我们回顾了 23 个人体组织和 6 种卵巢癌细胞系中几乎整个降解组的组织分布。为此，我们开发了 CLIP-CHIP™，这是一种基于 70 -mer 寡核苷酸平台的定制微阵列，用于专门分析在设计日期已知的 473 种活性人类蛋白酶、156 种蛋白酶抑制剂和 92 种非蛋白水解活性同源物的整个 repertoire 的转录本，每个转录本使用一个特定的 70-mer 寡核苷酸。使用 CLIP-CHIP™，我们在 104 个样本数据集中绘制了 23 种不同人体组织和 6 种卵巢癌细胞系中蛋白酶及其抑制剂的表达谱。层次聚类分析表明，表达谱根据其解剖位置、细胞组成、生理功能和来源的胚层聚类。人类卵巢癌细胞系根据恶性程度聚类。110 种蛋白酶和 42 种抑制剂具有组织特异性（1 至 3 种组织）。在这 110 种蛋白酶中，有 69%（74 种）主要存在于细胞外，30%（34 种）存在于细胞内，1%（1 种）存在于膜内。值得注意的是，565 种人类蛋白酶中有 35%（197 种）和 156 种抑制剂中有 30%（47 种）在所有 23 种组织中普遍表达；27%（155 种）的蛋白酶和 21%（32 种）的抑制剂在 4-20 种组织中广泛表达。我们的数据集为社区提供了一个有价值的资源，用于比较正常人体组织中蛋白酶和抑制剂的相对表达，并可用于与疾病组织（如卵巢癌）进行比较，以破译发病机制并辅助药物开发。本文是由 Stefan Rose-John 编辑的特刊“蛋白酶解作为病理生理学中的调节事件”的一部分。
