Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease

• Published in: Toxins Vol. 13; no. 8; p. 568
• Main Authors: Lu, Yi-Jhu, Wu, Ya-Ju, Chen, Lu-Jen, Ko, Bor-Sheng, Chang, Tzu-Ching, Wu, Yi-Ju, Liang, Shu-Man, Jan, Yee-Jee, Liou, Jun-Yang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15.08.2021; MDPI
• Subjects: Adult; Aged; Aged, 80 and over; Ammonium; ammonium pyrrolidinedithiocarbamate; Antioxidants; Aristolochic acid; Cancer; chronic kidney disease; Creatinine; Detoxification; Diabetes; Female; Fibrosis; Growth factors; Humans; Hypoxia; Immunohistochemistry; Injection; Kidney diseases; Kidney Tubules, Proximal - metabolism; Kidney Tubules, Proximal - physiopathology; Kidneys; Male; Metallothionein; Metallothionein - adverse effects; Metallothionein - metabolism; metallothionein-I/II; Middle Aged; Nephropathy; Proteins; Proximal tubules; Renal function; Renal Insufficiency, Chronic - chemically induced; Renal Insufficiency, Chronic - metabolism; Renal Insufficiency, Chronic - physiopathology; Urea; Young Adult; metallothionein-I/II; nephropathy; chronic kidney disease; ammonium pyrrolidinedithiocarbamate; aristolochic acid
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins13080568

Chronic kidney disease (CKD) is a commonly occurring complex renal syndrome that causes overall mortality in many diseases. The clinical manifestations of CKD include renal tubulointerstitial fibrosis and loss of renal function. Metallothionein-I/II (MT-I/II) is potentially expressed in the liver and kidney, and possesses antioxidant and metal detoxification properties. However, whether MT-I/II expression is associated with the prognosis of nephropathy remains unknown. In this study, we investigated the MT-I/II level in human CKD, using immunohistochemistry. MT-I/II is located on the proximal tubules and is notably reduced in patients with CKD. MT-I/II expression was significantly correlated with the functional and histological grades of CKD. In an aristolochic acid (AAI)-induced nephropathy mouse model, MT-I/II was abundantly increased after AAI injection for 7 days, but decreased subsequently compared to that induced in the acute phase when injected with AAI for 28 days. Furthermore, we found that ammonium pyrrolidinedithiocarbamate (PDTC) restored AAI-induced MT-I/II reduction in HK2 cells. The injection of PDTC ameliorated AAI-induced renal tubulointerstitial fibrosis and reduced the concentrations of blood urea nitrogen and creatinine in mouse sera. Taken together, our results indicate that MT-I/II reduction is associated with advanced CKD, and the retention of renal MT-I/II is a potential therapeutic strategy for CKD.