Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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
_version_ 1783709433840271360
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
work_keys_str_mv AT blessingnatalyaa lackofapol1inproximaltubulesofnormalhumankidneysandproteinuricapol1transgenicmousekidneys
AT wuzhenzhen lackofapol1inproximaltubulesofnormalhumankidneysandproteinuricapol1transgenicmousekidneys
AT madhavansethum lackofapol1inproximaltubulesofnormalhumankidneysandproteinuricapol1transgenicmousekidneys
AT choyjonathanw lackofapol1inproximaltubulesofnormalhumankidneysandproteinuricapol1transgenicmousekidneys
AT chenmichelle lackofapol1inproximaltubulesofnormalhumankidneysandproteinuricapol1transgenicmousekidneys
AT shinmyungk lackofapol1inproximaltubulesofnormalhumankidneysandproteinuricapol1transgenicmousekidneys
AT hoekmaarten lackofapol1inproximaltubulesofnormalhumankidneysandproteinuricapol1transgenicmousekidneys
AT sedorjohnr lackofapol1inproximaltubulesofnormalhumankidneysandproteinuricapol1transgenicmousekidneys
AT otoolejohnf lackofapol1inproximaltubulesofnormalhumankidneysandproteinuricapol1transgenicmousekidneys
AT bruggemanlesliea lackofapol1inproximaltubulesofnormalhumankidneysandproteinuricapol1transgenicmousekidneys