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Article

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

1
Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan 350, Taiwan
2
Department of Pathology, Chi Mei Medical Center, Liouying, Tainan 736, Taiwan
3
Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan
4
Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei 106, Taiwan
5
Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
6
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this study.
Toxins 2021, 13(8), 568; https://doi.org/10.3390/toxins13080568
Received: 4 May 2021 / Revised: 2 August 2021 / Accepted: 12 August 2021 / Published: 15 August 2021
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. View Full-Text
Keywords: ammonium pyrrolidinedithiocarbamate; aristolochic acid; chronic kidney disease; metallothionein-I/II; nephropathy ammonium pyrrolidinedithiocarbamate; aristolochic acid; chronic kidney disease; metallothionein-I/II; nephropathy
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MDPI and ACS Style

Lu, Y.-J.; Wu, Y.-J.; Chen, L.-J.; Ko, B.-S.; Chang, T.-C.; Wu, Y.-J.; Liang, S.-M.; Jan, Y.-J.; Liou, J.-Y. Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease. Toxins 2021, 13, 568. https://doi.org/10.3390/toxins13080568

AMA Style

Lu Y-J, Wu Y-J, Chen L-J, Ko B-S, Chang T-C, Wu Y-J, Liang S-M, Jan Y-J, Liou J-Y. Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease. Toxins. 2021; 13(8):568. https://doi.org/10.3390/toxins13080568

Chicago/Turabian Style

Lu, Yi-Jhu, Ya-Ju Wu, Lu-Jen Chen, Bor-Sheng Ko, Tzu-Ching Chang, Yi-Ju Wu, Shu-Man Liang, Yee-Jee Jan, and Jun-Yang Liou. 2021. "Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease" Toxins 13, no. 8: 568. https://doi.org/10.3390/toxins13080568

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