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

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 an...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402552/
https://www.ncbi.nlm.nih.gov/pubmed/34437439
http://dx.doi.org/10.3390/toxins13080568
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author 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
author_facet 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
author_sort Lu, Yi-Jhu
collection PubMed
description 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.
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spelling pubmed-84025522021-08-29 Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease 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 Toxins (Basel) Article 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. MDPI 2021-08-15 /pmc/articles/PMC8402552/ /pubmed/34437439 http://dx.doi.org/10.3390/toxins13080568 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease
title Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease
title_full Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease
title_fullStr Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease
title_full_unstemmed Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease
title_short Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease
title_sort reduced expression of metallothionein-i/ii in renal proximal tubules is associated with advanced chronic kidney disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402552/
https://www.ncbi.nlm.nih.gov/pubmed/34437439
http://dx.doi.org/10.3390/toxins13080568
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