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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2016
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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. |
format | Online Article Text |
id | pubmed-5101904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
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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