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...
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oai:doaj.org-article:fd5027d0c5714bc48fd1f7b797f2cb732021-12-02T20:10:31ZLack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys.1932-620310.1371/journal.pone.0253197https://doaj.org/article/fd5027d0c5714bc48fd1f7b797f2cb732021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253197https://doaj.org/toc/1932-6203The 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.Natalya A BlessingZhenzhen WuSethu M MadhavanJonathan W ChoyMichelle ChenMyung K ShinMaarten HoekJohn R SedorJohn F O'TooleLeslie A BruggemanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0253197 (2021) |
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Medicine R Science Q |
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Medicine R Science Q Natalya A Blessing Zhenzhen Wu Sethu M Madhavan Jonathan W Choy Michelle Chen Myung K Shin Maarten Hoek John R Sedor John F O'Toole Leslie A Bruggeman Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys. |
| 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 |
article |
| author |
Natalya A Blessing Zhenzhen Wu Sethu M Madhavan Jonathan W Choy Michelle Chen Myung K Shin Maarten Hoek John R Sedor John F O'Toole Leslie A Bruggeman |
| author_facet |
Natalya A Blessing Zhenzhen Wu Sethu M Madhavan Jonathan W Choy Michelle Chen Myung K Shin Maarten Hoek John R Sedor John F O'Toole Leslie A Bruggeman |
| author_sort |
Natalya A Blessing |
| title |
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_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_sort |
lack of apol1 in proximal tubules of normal human kidneys and proteinuric apol1 transgenic mouse kidneys. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/fd5027d0c5714bc48fd1f7b797f2cb73 |
| work_keys_str_mv |
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