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Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1

Chronic renal allograft dysfunction (CRAD) is the most common cause of graft failure following renal transplantation. However, the underlying mechanisms remain to be fully elucidated. Immunosuppressants and hyperlipidemia are associated with renal fibrosis following long-term use. The present study...

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Autores principales: Deng, Shi, Jin, Tao, Zhang, Li, Bu, Hong, Zhang, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101904/
https://www.ncbi.nlm.nih.gov/pubmed/27633115
http://dx.doi.org/10.3892/mmr.2016.5735
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author Deng, Shi
Jin, Tao
Zhang, Li
Bu, Hong
Zhang, Peng
author_facet Deng, Shi
Jin, Tao
Zhang, Li
Bu, Hong
Zhang, Peng
author_sort Deng, Shi
collection PubMed
description Chronic renal allograft dysfunction (CRAD) is the most common cause of graft failure following renal transplantation. However, the underlying mechanisms remain to be fully elucidated. Immunosuppressants and hyperlipidemia are associated with renal fibrosis following long-term use. The present study aimed to determine the effects of tacrolimus (FK506) and lipid metabolism disorder on CRAD. In vitro and in vivo models were used for this investigation. Cells of the mouse proximal renal tubular epithelial cell strain, NRK-52E, were cultured either with oxidized low-density lipoprotein (ox-LDL), FK506, ox-LDL combined with FK506, or vehicle, respectively. Changes in cell morphology and changes in the levels of lectin-like ox-LDL receptor-1 (LOX-1), reactive oxygen species (ROS), hydrogen peroxide and fibrosis-associated genes were evaluated at 24, 48 and 72 h. In separate experiment, total of 60 Sprague-Dawley rats were divided randomly into four groups, which included a high-fat group, FK506 group, high-fat combined with FK506 group, and control group. After 2, 4 and 8 weeks, the serum lipid levels, the levels of ox-LDL, ROS, and the expression levels of transforming growth factor (TGF)-β1 and connective tissue growth factor were determined. The in vitro and in vivo models revealed that lipid metabolism disorder and FK506 caused oxidative stress and a fibrogenic response. In addition, decreased levels of LOX-1 markedly reduced the levels of TGF-β1 in the in vitro model. Taken together, FK506 and dyslipidemia were found to be associated with CRAD following transplantation.
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spelling pubmed-51019042016-11-22 Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1 Deng, Shi Jin, Tao Zhang, Li Bu, Hong Zhang, Peng Mol Med Rep Articles Chronic renal allograft dysfunction (CRAD) is the most common cause of graft failure following renal transplantation. However, the underlying mechanisms remain to be fully elucidated. Immunosuppressants and hyperlipidemia are associated with renal fibrosis following long-term use. The present study aimed to determine the effects of tacrolimus (FK506) and lipid metabolism disorder on CRAD. In vitro and in vivo models were used for this investigation. Cells of the mouse proximal renal tubular epithelial cell strain, NRK-52E, were cultured either with oxidized low-density lipoprotein (ox-LDL), FK506, ox-LDL combined with FK506, or vehicle, respectively. Changes in cell morphology and changes in the levels of lectin-like ox-LDL receptor-1 (LOX-1), reactive oxygen species (ROS), hydrogen peroxide and fibrosis-associated genes were evaluated at 24, 48 and 72 h. In separate experiment, total of 60 Sprague-Dawley rats were divided randomly into four groups, which included a high-fat group, FK506 group, high-fat combined with FK506 group, and control group. After 2, 4 and 8 weeks, the serum lipid levels, the levels of ox-LDL, ROS, and the expression levels of transforming growth factor (TGF)-β1 and connective tissue growth factor were determined. The in vitro and in vivo models revealed that lipid metabolism disorder and FK506 caused oxidative stress and a fibrogenic response. In addition, decreased levels of LOX-1 markedly reduced the levels of TGF-β1 in the in vitro model. Taken together, FK506 and dyslipidemia were found to be associated with CRAD following transplantation. D.A. Spandidos 2016-11 2016-09-13 /pmc/articles/PMC5101904/ /pubmed/27633115 http://dx.doi.org/10.3892/mmr.2016.5735 Text en Copyright: © Deng et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Deng, Shi
Jin, Tao
Zhang, Li
Bu, Hong
Zhang, Peng
Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1
title Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1
title_full Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1
title_fullStr Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1
title_full_unstemmed Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1
title_short Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1
title_sort mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-ldl and its receptor, lox-1
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101904/
https://www.ncbi.nlm.nih.gov/pubmed/27633115
http://dx.doi.org/10.3892/mmr.2016.5735
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