Inhibiting Transglutaminase 2 Mediates Kidney Fibrosis via Anti-Apoptosis

Biomedicines

Yejin Choi¹  Kyu-Hyeon Kim¹  Areum Seo¹  Seung-Hee Yang¹  Jong-Joo Moon¹  Soie Kwon²  Yong-Chul Kim²  Yon-Su Kim²  Dong-Ki Kim² 

[1] Biomedical Research Institute, Seoul National University, Seoul 03080, Korea;Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea;

关键词: transglutaminase 2;    chronic kidney disease;    cystamine;    apoptosis;    fibrosis;   

DOI  :  10.3390/biomedicines10061345

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown