Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Chikusa, Nagoya, 464-8601, Japan.
Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Chikusa, Nagoya, 464-8601, Japan.
Anal Biochem. 2020 Sep 1;604:113629. doi: 10.1016/j.ab.2020.113629. Epub 2020 Feb 13.
The transglutaminase (TGase) family consists of eight isozymes that catalyze Ca-dependent crosslink formation between glutamine and lysine residues of proteins. In the pathogenesis of various chronic diseases, among the TGase isozymes, TG2 in particular is upregulated and contributes to a critical role in fibrosis development and progression via the stabilization of extracellular matrix proteins and activation of TGF-β. Although TG2 has been considered a key enzyme in fibrosis, the causative role of TG2 and involvement of other isozymes remain unclear. We have recently developed a comprehensive analysis method targeting the isozyme-specific substrates of TGase in liver and kidney fibrosis. In this review article, we introduce a previously developed method for determining the activity and tissue distribution of TGase and for the detecting and identification of TGase substrates in an isozyme-specific manner. Using our comprehensive analysis method, we newly characterized the overlapping profile data regarding potential substrates of TG1 and TG2 that have been identified in liver and kidney fibrosis to date. Our results obtained by comparing the specificity and similarity of potential TGase substrates between different tissue fibrosis models provide a deeper understanding regarding the specific and common pathways in disease pathogenesis and progression.
转谷氨酰胺酶（TGase）家族由 8 种同工酶组成，可催化蛋白质中谷氨酰胺和赖氨酸残基之间 Ca2+依赖性的交联形成。在各种慢性疾病的发病机制中，同工酶中 TG2 的表达上调尤为明显，并通过稳定细胞外基质蛋白和激活 TGF-β，在纤维化的发展和进展中发挥关键作用。尽管 TG2 已被认为是纤维化的关键酶，但 TG2 的因果作用和其他同工酶的参与仍不清楚。我们最近开发了一种针对肝纤维化和肾纤维化中同工酶特异性底物的综合分析方法。在这篇综述文章中，我们介绍了一种以前开发的方法，用于测定 TGase 的活性和组织分布，并以同工酶特异性的方式检测和鉴定 TGase 底物。使用我们的综合分析方法，我们对迄今为止在肝纤维化和肾纤维化中鉴定的 TG1 和 TG2 的潜在底物的重叠谱数据进行了新的特征描述。通过比较不同组织纤维化模型中潜在 TGase 底物的特异性和相似性，我们获得的结果加深了对疾病发病机制和进展中特定和共同途径的理解。
