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Cellular Cholesterol Transport Proteins in Diabetic Nephropathy

BACKGROUND: Lipid accumulation has been shown to accelerate renal injury, and the intracellular accumulation of lipids may be caused by alterations in synthesis as well as lipid uptake and efflux. We have investigated the role of cellular cholesterol transport proteins including adenosine triphospha...

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Autores principales: Tsun, Joseph G. S., Yung, Susan, Chau, Mel K. M., Shiu, Sammy W. M., Chan, Tak Mao, Tan, Kathryn C. B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4152117/
https://www.ncbi.nlm.nih.gov/pubmed/25181357
http://dx.doi.org/10.1371/journal.pone.0105787
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author Tsun, Joseph G. S.
Yung, Susan
Chau, Mel K. M.
Shiu, Sammy W. M.
Chan, Tak Mao
Tan, Kathryn C. B.
author_facet Tsun, Joseph G. S.
Yung, Susan
Chau, Mel K. M.
Shiu, Sammy W. M.
Chan, Tak Mao
Tan, Kathryn C. B.
author_sort Tsun, Joseph G. S.
collection PubMed
description BACKGROUND: Lipid accumulation has been shown to accelerate renal injury, and the intracellular accumulation of lipids may be caused by alterations in synthesis as well as lipid uptake and efflux. We have investigated the role of cellular cholesterol transport proteins including adenosine triphosphate binding cassette transporter A1 (ABCA1), G1 (ABCG1) and scavenger receptor class B type I (SR-BI) in diabetic nephropathy. METHODS: Protein expression and the ability to mediate cholesterol efflux of ABCA1, ABCG1 and SR-BI was determined in human renal mesangial cells and proximal tubular epithelial cells cultured under normal or high glucose conditions. Renal expression of these cholesterol transporters was examined in a murine model of streptozotocin-induced type 1 diabetes. RESULTS: ABCA1, ABCG1 and SR-BI were expressed in both human renal mesangial cells and proximal tubular epithelial cells, and mediated cholesterol efflux to apolipoprotein AI and HDL. In vitro, hyperglycemia reduced the expression and the ability to mediate cholesterol efflux of all three cholesterol transporters (p<0.05). In vivo studies showed that intra-renal accumulation of lipids was increased in diabetic mice, particularly in mice with nephropathy. This was associated with a significant reduction in the expression of ABCA1, ABCG1 and SR-BI in the kidneys. These changes were already seen in diabetic mice without nephropathy and preceded the development of nephropathy. Diabetic mice with nephropathy had the lowest level of these cholesterol transporters. CONCLUSION: Inducing diabetes with streptozotocin significantly reduced renal expression of ABCA1, ABCG1 and SR-BI. Defects in cholesterol export pathway in renal cells could therefore promote cholesterol accumulation and might contribute to the development of diabetic nephropathy.
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spelling pubmed-41521172014-09-05 Cellular Cholesterol Transport Proteins in Diabetic Nephropathy Tsun, Joseph G. S. Yung, Susan Chau, Mel K. M. Shiu, Sammy W. M. Chan, Tak Mao Tan, Kathryn C. B. PLoS One Research Article BACKGROUND: Lipid accumulation has been shown to accelerate renal injury, and the intracellular accumulation of lipids may be caused by alterations in synthesis as well as lipid uptake and efflux. We have investigated the role of cellular cholesterol transport proteins including adenosine triphosphate binding cassette transporter A1 (ABCA1), G1 (ABCG1) and scavenger receptor class B type I (SR-BI) in diabetic nephropathy. METHODS: Protein expression and the ability to mediate cholesterol efflux of ABCA1, ABCG1 and SR-BI was determined in human renal mesangial cells and proximal tubular epithelial cells cultured under normal or high glucose conditions. Renal expression of these cholesterol transporters was examined in a murine model of streptozotocin-induced type 1 diabetes. RESULTS: ABCA1, ABCG1 and SR-BI were expressed in both human renal mesangial cells and proximal tubular epithelial cells, and mediated cholesterol efflux to apolipoprotein AI and HDL. In vitro, hyperglycemia reduced the expression and the ability to mediate cholesterol efflux of all three cholesterol transporters (p<0.05). In vivo studies showed that intra-renal accumulation of lipids was increased in diabetic mice, particularly in mice with nephropathy. This was associated with a significant reduction in the expression of ABCA1, ABCG1 and SR-BI in the kidneys. These changes were already seen in diabetic mice without nephropathy and preceded the development of nephropathy. Diabetic mice with nephropathy had the lowest level of these cholesterol transporters. CONCLUSION: Inducing diabetes with streptozotocin significantly reduced renal expression of ABCA1, ABCG1 and SR-BI. Defects in cholesterol export pathway in renal cells could therefore promote cholesterol accumulation and might contribute to the development of diabetic nephropathy. Public Library of Science 2014-09-02 /pmc/articles/PMC4152117/ /pubmed/25181357 http://dx.doi.org/10.1371/journal.pone.0105787 Text en © 2014 Tsun et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tsun, Joseph G. S.
Yung, Susan
Chau, Mel K. M.
Shiu, Sammy W. M.
Chan, Tak Mao
Tan, Kathryn C. B.
Cellular Cholesterol Transport Proteins in Diabetic Nephropathy
title Cellular Cholesterol Transport Proteins in Diabetic Nephropathy
title_full Cellular Cholesterol Transport Proteins in Diabetic Nephropathy
title_fullStr Cellular Cholesterol Transport Proteins in Diabetic Nephropathy
title_full_unstemmed Cellular Cholesterol Transport Proteins in Diabetic Nephropathy
title_short Cellular Cholesterol Transport Proteins in Diabetic Nephropathy
title_sort cellular cholesterol transport proteins in diabetic nephropathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4152117/
https://www.ncbi.nlm.nih.gov/pubmed/25181357
http://dx.doi.org/10.1371/journal.pone.0105787
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