Moon Jong-Joo, Choi Yejin, Kim Kyu-Hyeon, Seo Areum, Kwon Soie, Kim Yong-Chul, Kim Dong-Ki, Kim Yon-Su, Yang Seung-Hee
Biomedical Research Institute, Seoul National University, Seoul 03080, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.
Biomedicines. 2022 Jun 7;10(6):1345. doi: 10.3390/biomedicines10061345.
Transglutaminase 2 (TG2) is a calcium-dependent transamidating acyltransferase enzyme of the protein-glutamine γ-glutamyltransferase family implicated in kidney injury. In this study, we identified associations between TG2 and chronic kidney disease (CKD) identified by visualizing TG2 in kidney biopsy samples derived from CKD patients using immunohistochemistry and measuring the plasma TG2 concentrations. Our study revealed a connection between TG2 and the pathological markers of kidney disease. We showed high plasma TG2 levels in samples from patients with advanced CKD. In addition, we observed an increase in TG2 expression in tissues concomitant with advanced CKD in human samples. Moreover, we investigated the effect of TG2 inhibition on kidney injury using cystamine, a well-known competitive inhibitor of TG2. TG2 inhibition reduced apoptosis and accumulation of extracellular molecules (ECM) such as fibronectin and pro-inflammatory cytokine IL-8. Collectively, the increased expression of TG2 that was observed in advanced CKD, hence inhibiting TG2 activity, could protect kidney cells from ECM molecule accumulation, apoptosis, and inflammatory responses, thereby preventing kidney fibrosis.
转谷氨酰胺酶2（TG2）是一种钙依赖性转酰胺酰基转移酶，属于蛋白质-谷氨酰胺γ-谷氨酰转移酶家族，与肾损伤有关。在本研究中，我们通过免疫组织化学观察慢性肾脏病（CKD）患者肾活检样本中的TG2，并测量血浆TG2浓度，确定了TG2与CKD之间的关联。我们的研究揭示了TG2与肾脏疾病病理标志物之间的联系。我们发现晚期CKD患者样本中的血浆TG2水平较高。此外，我们观察到在人类样本中，随着CKD进展，组织中TG2表达增加。此外，我们使用胱胺（一种著名的TG2竞争性抑制剂）研究了TG2抑制对肾损伤的影响。TG2抑制减少了细胞凋亡以及细胞外分子（如纤连蛋白和促炎细胞因子IL-8）的积累。总体而言，在晚期CKD中观察到的TG2表达增加，因此抑制TG2活性，可以保护肾细胞免受细胞外基质分子积累、细胞凋亡和炎症反应的影响，从而预防肾纤维化。
