Loading…

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...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2021-06, Vol.16 (6), p.e0253197-e0253197
Main Authors: 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
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c640t-251cffd8994789918062c6f896a8993e1587339d9d716e1e866d70754937036e3
cites cdi_FETCH-LOGICAL-c640t-251cffd8994789918062c6f896a8993e1587339d9d716e1e866d70754937036e3
container_end_page e0253197
container_issue 6
container_start_page e0253197
container_title PloS one
container_volume 16
creator 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
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.
doi_str_mv 10.1371/journal.pone.0253197
format article
fullrecord <record><control><sourceid>gale_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_fd5027d0c5714bc48fd1f7b797f2cb73</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A665559744</galeid><doaj_id>oai_doaj_org_article_fd5027d0c5714bc48fd1f7b797f2cb73</doaj_id><sourcerecordid>A665559744</sourcerecordid><originalsourceid>FETCH-LOGICAL-c640t-251cffd8994789918062c6f896a8993e1587339d9d716e1e866d70754937036e3</originalsourceid><addsrcrecordid>eNqNkluLEzEUx4Mo7lr9BiIDguhDa26TzLwIZfFSKFS8vYY0lzbdmaSbzMjutzdjZ5cO-CCBZHLyO__JOfkD8BLBBSIcvT-EPnrZLI7BmwXEJUE1fwQuUU3wnGFIHp99X4BnKR0gLEnF2FNwQSgiVQ3xJdivpbougi2WXzdrVDhfHGO4da1siq7f9o1Jw6EPcYjs-1b64tppb-5SIb0e4M4430enRoUuSp92xudAG_pk7vHn4ImVTTIvxnUGfn76-OPqy3y9-by6Wq7nilHYzXGJlLW6qmvK84QqyLBitqqZzFtiUFlxQmpda46YQSbXoznkJa0Jh4QZMgOrk64O8iCOMZcS70SQTvwNhLgTMnZONUZYXULMNVQlR3SraGU1snzLa26x2ubfzMCHk9ax37ZGK-Nzdc1EdHri3V7swm9RYYQwrLLA21EghpvepE60LinTNNKb3ByBS0ooZTg_1Ay8PqE7ma_mvA1ZUQ24WDJWlmXNKc3U4h9UHtq0TmUnWJfjk4R3k4TMdOa228k-JbH6_u3_2c2vKfvmjN0b2XT7FJq-c8GnKUhPoIohpWjsQ_sQFIORxWhkMRhZjEbOaa_OW_-QdO9c8gd7F-4O</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2543446219</pqid></control><display><type>article</type><title>Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys</title><source>Publicly Available Content Database</source><source>PubMed Central</source><creator>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</creator><contributor>Dryer, Stuart E.</contributor><creatorcontrib>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 ; Dryer, Stuart E.</creatorcontrib><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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0253197</identifier><identifier>PMID: 34138902</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alleles ; Analysis ; Animal models in research ; Animals ; Apolipoprotein L1 - genetics ; Apolipoprotein L1 - metabolism ; Biology and Life Sciences ; Endothelial Cells - metabolism ; Engineering and Technology ; Evaluation ; Genetic aspects ; Genetic engineering ; Genetic polymorphisms ; Humans ; Kidney ; Kidney Tubules, Proximal - metabolism ; Kidneys ; Liver - metabolism ; Medicine and Health Sciences ; Mice ; Mice, Transgenic ; Podocytes - metabolism ; Proteinuria - genetics ; Proteinuria - metabolism ; Research and Analysis Methods</subject><ispartof>PloS one, 2021-06, Vol.16 (6), p.e0253197-e0253197</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Blessing et al 2021 Blessing et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c640t-251cffd8994789918062c6f896a8993e1587339d9d716e1e866d70754937036e3</citedby><cites>FETCH-LOGICAL-c640t-251cffd8994789918062c6f896a8993e1587339d9d716e1e866d70754937036e3</cites><orcidid>0000-0001-5874-705X ; 0000-0002-5237-1626</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211208/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211208/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,37013,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34138902$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Dryer, Stuart E.</contributor><creatorcontrib>Blessing, Natalya A</creatorcontrib><creatorcontrib>Wu, Zhenzhen</creatorcontrib><creatorcontrib>Madhavan, Sethu M</creatorcontrib><creatorcontrib>Choy, Jonathan W</creatorcontrib><creatorcontrib>Chen, Michelle</creatorcontrib><creatorcontrib>Shin, Myung K</creatorcontrib><creatorcontrib>Hoek, Maarten</creatorcontrib><creatorcontrib>Sedor, John R</creatorcontrib><creatorcontrib>O'Toole, John F</creatorcontrib><creatorcontrib>Bruggeman, Leslie A</creatorcontrib><title>Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Alleles</subject><subject>Analysis</subject><subject>Animal models in research</subject><subject>Animals</subject><subject>Apolipoprotein L1 - genetics</subject><subject>Apolipoprotein L1 - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Endothelial Cells - metabolism</subject><subject>Engineering and Technology</subject><subject>Evaluation</subject><subject>Genetic aspects</subject><subject>Genetic engineering</subject><subject>Genetic polymorphisms</subject><subject>Humans</subject><subject>Kidney</subject><subject>Kidney Tubules, Proximal - metabolism</subject><subject>Kidneys</subject><subject>Liver - metabolism</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Podocytes - metabolism</subject><subject>Proteinuria - genetics</subject><subject>Proteinuria - metabolism</subject><subject>Research and Analysis Methods</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNqNkluLEzEUx4Mo7lr9BiIDguhDa26TzLwIZfFSKFS8vYY0lzbdmaSbzMjutzdjZ5cO-CCBZHLyO__JOfkD8BLBBSIcvT-EPnrZLI7BmwXEJUE1fwQuUU3wnGFIHp99X4BnKR0gLEnF2FNwQSgiVQ3xJdivpbougi2WXzdrVDhfHGO4da1siq7f9o1Jw6EPcYjs-1b64tppb-5SIb0e4M4430enRoUuSp92xudAG_pk7vHn4ImVTTIvxnUGfn76-OPqy3y9-by6Wq7nilHYzXGJlLW6qmvK84QqyLBitqqZzFtiUFlxQmpda46YQSbXoznkJa0Jh4QZMgOrk64O8iCOMZcS70SQTvwNhLgTMnZONUZYXULMNVQlR3SraGU1snzLa26x2ubfzMCHk9ax37ZGK-Nzdc1EdHri3V7swm9RYYQwrLLA21EghpvepE60LinTNNKb3ByBS0ooZTg_1Ay8PqE7ma_mvA1ZUQ24WDJWlmXNKc3U4h9UHtq0TmUnWJfjk4R3k4TMdOa228k-JbH6_u3_2c2vKfvmjN0b2XT7FJq-c8GnKUhPoIohpWjsQ_sQFIORxWhkMRhZjEbOaa_OW_-QdO9c8gd7F-4O</recordid><startdate>20210617</startdate><enddate>20210617</enddate><creator>Blessing, Natalya A</creator><creator>Wu, Zhenzhen</creator><creator>Madhavan, Sethu M</creator><creator>Choy, Jonathan W</creator><creator>Chen, Michelle</creator><creator>Shin, Myung K</creator><creator>Hoek, Maarten</creator><creator>Sedor, John R</creator><creator>O'Toole, John F</creator><creator>Bruggeman, Leslie A</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5874-705X</orcidid><orcidid>https://orcid.org/0000-0002-5237-1626</orcidid></search><sort><creationdate>20210617</creationdate><title>Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c640t-251cffd8994789918062c6f896a8993e1587339d9d716e1e866d70754937036e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alleles</topic><topic>Analysis</topic><topic>Animal models in research</topic><topic>Animals</topic><topic>Apolipoprotein L1 - genetics</topic><topic>Apolipoprotein L1 - metabolism</topic><topic>Biology and Life Sciences</topic><topic>Endothelial Cells - metabolism</topic><topic>Engineering and Technology</topic><topic>Evaluation</topic><topic>Genetic aspects</topic><topic>Genetic engineering</topic><topic>Genetic polymorphisms</topic><topic>Humans</topic><topic>Kidney</topic><topic>Kidney Tubules, Proximal - metabolism</topic><topic>Kidneys</topic><topic>Liver - metabolism</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Podocytes - metabolism</topic><topic>Proteinuria - genetics</topic><topic>Proteinuria - metabolism</topic><topic>Research and Analysis Methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Blessing, Natalya A</creatorcontrib><creatorcontrib>Wu, Zhenzhen</creatorcontrib><creatorcontrib>Madhavan, Sethu M</creatorcontrib><creatorcontrib>Choy, Jonathan W</creatorcontrib><creatorcontrib>Chen, Michelle</creatorcontrib><creatorcontrib>Shin, Myung K</creatorcontrib><creatorcontrib>Hoek, Maarten</creatorcontrib><creatorcontrib>Sedor, John R</creatorcontrib><creatorcontrib>O'Toole, John F</creatorcontrib><creatorcontrib>Bruggeman, Leslie A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints database</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Blessing, Natalya A</au><au>Wu, Zhenzhen</au><au>Madhavan, Sethu M</au><au>Choy, Jonathan W</au><au>Chen, Michelle</au><au>Shin, Myung K</au><au>Hoek, Maarten</au><au>Sedor, John R</au><au>O'Toole, John F</au><au>Bruggeman, Leslie A</au><au>Dryer, Stuart E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-06-17</date><risdate>2021</risdate><volume>16</volume><issue>6</issue><spage>e0253197</spage><epage>e0253197</epage><pages>e0253197-e0253197</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34138902</pmid><doi>10.1371/journal.pone.0253197</doi><tpages>e0253197</tpages><orcidid>https://orcid.org/0000-0001-5874-705X</orcidid><orcidid>https://orcid.org/0000-0002-5237-1626</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2021-06, Vol.16 (6), p.e0253197-e0253197
issn 1932-6203
1932-6203
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_fd5027d0c5714bc48fd1f7b797f2cb73
source Publicly Available Content Database; PubMed Central
subjects Alleles
Analysis
Animal models in research
Animals
Apolipoprotein L1 - genetics
Apolipoprotein L1 - metabolism
Biology and Life Sciences
Endothelial Cells - metabolism
Engineering and Technology
Evaluation
Genetic aspects
Genetic engineering
Genetic polymorphisms
Humans
Kidney
Kidney Tubules, Proximal - metabolism
Kidneys
Liver - metabolism
Medicine and Health Sciences
Mice
Mice, Transgenic
Podocytes - metabolism
Proteinuria - genetics
Proteinuria - metabolism
Research and Analysis Methods
title Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T20%3A03%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Lack%20of%20APOL1%20in%20proximal%20tubules%20of%20normal%20human%20kidneys%20and%20proteinuric%20APOL1%20transgenic%20mouse%20kidneys&rft.jtitle=PloS%20one&rft.au=Blessing,%20Natalya%20A&rft.date=2021-06-17&rft.volume=16&rft.issue=6&rft.spage=e0253197&rft.epage=e0253197&rft.pages=e0253197-e0253197&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0253197&rft_dat=%3Cgale_doaj_%3EA665559744%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c640t-251cffd8994789918062c6f896a8993e1587339d9d716e1e866d70754937036e3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2543446219&rft_id=info:pmid/34138902&rft_galeid=A665559744&rfr_iscdi=true