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Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys
The mechanism of pathogenesis associated with APOL1 polymorphisms and risk for non-diabetic chronic kidney disease (CKD) is not fully understood. Prior studies have minimized a causal role for the circulating APOL1 protein, thus efforts to understand kidney pathogenesis have focused on APOL1 express...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211208/ https://www.ncbi.nlm.nih.gov/pubmed/34138902 http://dx.doi.org/10.1371/journal.pone.0253197 |
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author | Blessing, Natalya A. Wu, Zhenzhen Madhavan, Sethu M. Choy, Jonathan W. Chen, Michelle Shin, Myung K. Hoek, Maarten Sedor, John R. O’Toole, John F. Bruggeman, Leslie A. |
author_facet | Blessing, Natalya A. Wu, Zhenzhen Madhavan, Sethu M. Choy, Jonathan W. Chen, Michelle Shin, Myung K. Hoek, Maarten Sedor, John R. O’Toole, John F. Bruggeman, Leslie A. |
author_sort | Blessing, Natalya A. |
collection | PubMed |
description | The mechanism of pathogenesis associated with APOL1 polymorphisms and risk for non-diabetic chronic kidney disease (CKD) is not fully understood. Prior studies have minimized a causal role for the circulating APOL1 protein, thus efforts to understand kidney pathogenesis have focused on APOL1 expressed in renal cells. Of the kidney cells reported to express APOL1, the proximal tubule expression patterns are inconsistent in published reports, and whether APOL1 is synthesized by the proximal tubule or possibly APOL1 protein in the blood is filtered and reabsorbed by the proximal tubule remains unclear. Using both protein and mRNA in situ methods, the kidney expression pattern of APOL1 was examined in normal human and APOL1 bacterial artificial chromosome transgenic mice with and without proteinuria. APOL1 protein and mRNA was detected in podocytes and endothelial cells, but not in tubular epithelia. In the setting of proteinuria, plasma APOL1 protein did not appear to be filtered or reabsorbed by the proximal tubule. A side-by-side examination of commercial antibodies used in prior studies suggest the original reports of APOL1 in proximal tubules likely reflects antibody non-specificity. As such, APOL1 expression in podocytes and endothelia should remain the focus for mechanistic studies in the APOL1-mediated kidney diseases. |
format | Online Article Text |
id | pubmed-8211208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-82112082021-06-29 Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys Blessing, Natalya A. Wu, Zhenzhen Madhavan, Sethu M. Choy, Jonathan W. Chen, Michelle Shin, Myung K. Hoek, Maarten Sedor, John R. O’Toole, John F. Bruggeman, Leslie A. PLoS One Research Article The mechanism of pathogenesis associated with APOL1 polymorphisms and risk for non-diabetic chronic kidney disease (CKD) is not fully understood. Prior studies have minimized a causal role for the circulating APOL1 protein, thus efforts to understand kidney pathogenesis have focused on APOL1 expressed in renal cells. Of the kidney cells reported to express APOL1, the proximal tubule expression patterns are inconsistent in published reports, and whether APOL1 is synthesized by the proximal tubule or possibly APOL1 protein in the blood is filtered and reabsorbed by the proximal tubule remains unclear. Using both protein and mRNA in situ methods, the kidney expression pattern of APOL1 was examined in normal human and APOL1 bacterial artificial chromosome transgenic mice with and without proteinuria. APOL1 protein and mRNA was detected in podocytes and endothelial cells, but not in tubular epithelia. In the setting of proteinuria, plasma APOL1 protein did not appear to be filtered or reabsorbed by the proximal tubule. A side-by-side examination of commercial antibodies used in prior studies suggest the original reports of APOL1 in proximal tubules likely reflects antibody non-specificity. As such, APOL1 expression in podocytes and endothelia should remain the focus for mechanistic studies in the APOL1-mediated kidney diseases. Public Library of Science 2021-06-17 /pmc/articles/PMC8211208/ /pubmed/34138902 http://dx.doi.org/10.1371/journal.pone.0253197 Text en © 2021 Blessing et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Blessing, Natalya A. Wu, Zhenzhen Madhavan, Sethu M. Choy, Jonathan W. Chen, Michelle Shin, Myung K. Hoek, Maarten Sedor, John R. O’Toole, John F. Bruggeman, Leslie A. Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys |
title | Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys |
title_full | Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys |
title_fullStr | Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys |
title_full_unstemmed | Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys |
title_short | Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys |
title_sort | lack of apol1 in proximal tubules of normal human kidneys and proteinuric apol1 transgenic mouse kidneys |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211208/ https://www.ncbi.nlm.nih.gov/pubmed/34138902 http://dx.doi.org/10.1371/journal.pone.0253197 |
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