Variant APOL1 protein in plasma associates with larger particles in humans and mouse models of kidney injury
Genetic variants in apolipoprotein L1 (APOL1), a protein that protects humans from infection with African trypanosomes, explain a substantial proportion of the excess risk of chronic kidney disease affecting individuals with sub-Saharan ancestry. The mechanisms by which risk variants damage kidney c...
Gespeichert in:
Veröffentlicht in: | PloS one 2022-10, Vol.17 (10), p.e0276649-e0276649 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | e0276649 |
---|---|
container_issue | 10 |
container_start_page | e0276649 |
container_title | PloS one |
container_volume | 17 |
creator | Andrews, Michael Yoshida, Teruhiko Henderson, Clark M Pflaum, Hannah McGregor, Ayako Lieberman, Joshua A de Boer, Ian H Vaisar, Tomas Himmelfarb, Jonathan Kestenbaum, Bryan Chung, Joon-Yong Hewitt, Stephen M Santo, Briana A Ginley, Brandon Sarder, Pinaki Rosenberg, Avi Z Murakami, Taichi Kopp, Jeffrey B Kuklenyik, Zsuzsanna Hoofnagle, Andrew N |
description | Genetic variants in apolipoprotein L1 (APOL1), a protein that protects humans from infection with African trypanosomes, explain a substantial proportion of the excess risk of chronic kidney disease affecting individuals with sub-Saharan ancestry. The mechanisms by which risk variants damage kidney cells remain incompletely understood. In preclinical models, APOL1 expressed in podocytes can lead to significant kidney injury. In humans, studies in kidney transplant suggest that the effects of APOL1 variants are predominantly driven by donor genotype. Less attention has been paid to a possible role for circulating APOL1 in kidney injury.
Using liquid chromatography-tandem mass spectrometry, the concentrations of APOL1 were measured in plasma and urine from participants in the Seattle Kidney Study. Asymmetric flow field-flow fractionation was used to evaluate the size of APOL1-containing lipoprotein particles in plasma. Transgenic mice that express wild-type or risk variant APOL1 from an albumin promoter were treated to cause kidney injury and evaluated for renal disease and pathology.
In human participants, urine concentrations of APOL1 were correlated with plasma concentrations and reduced kidney function. Risk variant APOL1 was enriched in larger particles. In mice, circulating risk variant APOL1-G1 promoted kidney damage and reduced podocyte density without renal expression of APOL1.
These results suggest that plasma APOL1 is dynamic and contributes to the progression of kidney disease in humans, which may have implications for treatment of APOL1-associated kidney disease and for kidney transplantation. |
doi_str_mv | 10.1371/journal.pone.0276649 |
format | Article |
fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2728052262</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A723878552</galeid><doaj_id>oai_doaj_org_article_1ad117934bd2419bb2282f1e40dd23a2</doaj_id><sourcerecordid>A723878552</sourcerecordid><originalsourceid>FETCH-LOGICAL-c585t-d3bed0491248d269887f74df2603203346b296bfc28d0cee114fe6c679cdc8d13</originalsourceid><addsrcrecordid>eNptkl2LEzEUhgdR3HX1H4gOCOJNa74mHzdCWfxYKKwX6m3IJJk2NZOMyYzSf2-6nV1aEUISkue857yHU1UvIVhCzOD7XZxSUH45xGCXADFKiXhUXUKB0YIigB-f3C-qZznvAGgwp_RpdYEpYgKJ5rLyP1RyKoz16uvtGtZDiqN1oS5r8Cr3qlY5R-3UaHP9x43b2qu0sakeVBqd9uW1oNupVyHXKpi6j1O2ZTfW5zp29U9ngt0XaDel_fPqSad8ti_m86r6_unjt-svi_Xt55vr1XqhG96MC4NbawAREBFuEBWcs44R0yEKcDGDCW2RoG2nETdAWwsh6SzVlAltNDcQX1Wvj7qDj1nOjcoSMcRBgxBFhbg5EiaqnRyS61Xay6icvHuIaSNngxIqAyETmLQGESjaFiGOOmgJMAZhddD6MGeb2t4abcOYlD8TPf8Jbis38bcUjYCg4UXg3SyQ4q_J5lH2LmvrvQq2tPOubkgYbGhB3_yD_t_dTG1UMeBCF0tefRCVK4YwZ7xpDtTbE2prlR-3OfppdDHkc5AcQZ1izsl2D94gkIdZvC9CHmZRzrNYwl6d9uUh6H748F8JVtuA</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2728052262</pqid></control><display><type>article</type><title>Variant APOL1 protein in plasma associates with larger particles in humans and mouse models of kidney injury</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Andrews, Michael ; Yoshida, Teruhiko ; Henderson, Clark M ; Pflaum, Hannah ; McGregor, Ayako ; Lieberman, Joshua A ; de Boer, Ian H ; Vaisar, Tomas ; Himmelfarb, Jonathan ; Kestenbaum, Bryan ; Chung, Joon-Yong ; Hewitt, Stephen M ; Santo, Briana A ; Ginley, Brandon ; Sarder, Pinaki ; Rosenberg, Avi Z ; Murakami, Taichi ; Kopp, Jeffrey B ; Kuklenyik, Zsuzsanna ; Hoofnagle, Andrew N</creator><creatorcontrib>Andrews, Michael ; Yoshida, Teruhiko ; Henderson, Clark M ; Pflaum, Hannah ; McGregor, Ayako ; Lieberman, Joshua A ; de Boer, Ian H ; Vaisar, Tomas ; Himmelfarb, Jonathan ; Kestenbaum, Bryan ; Chung, Joon-Yong ; Hewitt, Stephen M ; Santo, Briana A ; Ginley, Brandon ; Sarder, Pinaki ; Rosenberg, Avi Z ; Murakami, Taichi ; Kopp, Jeffrey B ; Kuklenyik, Zsuzsanna ; Hoofnagle, Andrew N</creatorcontrib><description>Genetic variants in apolipoprotein L1 (APOL1), a protein that protects humans from infection with African trypanosomes, explain a substantial proportion of the excess risk of chronic kidney disease affecting individuals with sub-Saharan ancestry. The mechanisms by which risk variants damage kidney cells remain incompletely understood. In preclinical models, APOL1 expressed in podocytes can lead to significant kidney injury. In humans, studies in kidney transplant suggest that the effects of APOL1 variants are predominantly driven by donor genotype. Less attention has been paid to a possible role for circulating APOL1 in kidney injury.
Using liquid chromatography-tandem mass spectrometry, the concentrations of APOL1 were measured in plasma and urine from participants in the Seattle Kidney Study. Asymmetric flow field-flow fractionation was used to evaluate the size of APOL1-containing lipoprotein particles in plasma. Transgenic mice that express wild-type or risk variant APOL1 from an albumin promoter were treated to cause kidney injury and evaluated for renal disease and pathology.
In human participants, urine concentrations of APOL1 were correlated with plasma concentrations and reduced kidney function. Risk variant APOL1 was enriched in larger particles. In mice, circulating risk variant APOL1-G1 promoted kidney damage and reduced podocyte density without renal expression of APOL1.
These results suggest that plasma APOL1 is dynamic and contributes to the progression of kidney disease in humans, which may have implications for treatment of APOL1-associated kidney disease and for kidney transplantation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0276649</identifier><identifier>PMID: 36279295</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Albumin ; Albumins ; Analysis ; Animal models ; Animals ; Apolipoprotein L1 - genetics ; Apolipoprotein L1 - metabolism ; Apolipoproteins ; Apolipoproteins - genetics ; Biology and Life Sciences ; Chromatography ; Chronic kidney failure ; Creatinine ; Damage ; Disease ; Disease Models, Animal ; Engineering and Technology ; Evaluation ; Fibroblasts ; Fractionation ; Genetic diversity ; Genetic engineering ; Genetic variance ; Genotype & phenotype ; Genotypes ; Growth factors ; Health aspects ; Health risks ; Humans ; Injuries ; Kidney - pathology ; Kidney diseases ; Kidney transplantation ; Kidneys ; Kinases ; Laboratory animals ; Liquid chromatography ; Mass spectrometry ; Mass spectroscopy ; Measurement ; Medicine and Health Sciences ; Methods ; Mice ; Mice, Transgenic ; Peptides ; Plasma ; Polymorphism ; Prevention ; Proteins ; Renal Insufficiency, Chronic - genetics ; Renal Insufficiency, Chronic - pathology ; Research and Analysis Methods ; Risk ; Risk factors ; Transgenic animals ; Transgenic mice ; Transplantation ; Urine</subject><ispartof>PloS one, 2022-10, Vol.17 (10), p.e0276649-e0276649</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c585t-d3bed0491248d269887f74df2603203346b296bfc28d0cee114fe6c679cdc8d13</citedby><cites>FETCH-LOGICAL-c585t-d3bed0491248d269887f74df2603203346b296bfc28d0cee114fe6c679cdc8d13</cites><orcidid>0000-0003-1958-909X ; 0000-0001-9801-7705 ; 0000-0002-2049-7347 ; 0000-0002-6449-0243 ; 0000-0002-7406-6606</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/PMC9591058/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9591058/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36279295$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Andrews, Michael</creatorcontrib><creatorcontrib>Yoshida, Teruhiko</creatorcontrib><creatorcontrib>Henderson, Clark M</creatorcontrib><creatorcontrib>Pflaum, Hannah</creatorcontrib><creatorcontrib>McGregor, Ayako</creatorcontrib><creatorcontrib>Lieberman, Joshua A</creatorcontrib><creatorcontrib>de Boer, Ian H</creatorcontrib><creatorcontrib>Vaisar, Tomas</creatorcontrib><creatorcontrib>Himmelfarb, Jonathan</creatorcontrib><creatorcontrib>Kestenbaum, Bryan</creatorcontrib><creatorcontrib>Chung, Joon-Yong</creatorcontrib><creatorcontrib>Hewitt, Stephen M</creatorcontrib><creatorcontrib>Santo, Briana A</creatorcontrib><creatorcontrib>Ginley, Brandon</creatorcontrib><creatorcontrib>Sarder, Pinaki</creatorcontrib><creatorcontrib>Rosenberg, Avi Z</creatorcontrib><creatorcontrib>Murakami, Taichi</creatorcontrib><creatorcontrib>Kopp, Jeffrey B</creatorcontrib><creatorcontrib>Kuklenyik, Zsuzsanna</creatorcontrib><creatorcontrib>Hoofnagle, Andrew N</creatorcontrib><title>Variant APOL1 protein in plasma associates with larger particles in humans and mouse models of kidney injury</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Genetic variants in apolipoprotein L1 (APOL1), a protein that protects humans from infection with African trypanosomes, explain a substantial proportion of the excess risk of chronic kidney disease affecting individuals with sub-Saharan ancestry. The mechanisms by which risk variants damage kidney cells remain incompletely understood. In preclinical models, APOL1 expressed in podocytes can lead to significant kidney injury. In humans, studies in kidney transplant suggest that the effects of APOL1 variants are predominantly driven by donor genotype. Less attention has been paid to a possible role for circulating APOL1 in kidney injury.
Using liquid chromatography-tandem mass spectrometry, the concentrations of APOL1 were measured in plasma and urine from participants in the Seattle Kidney Study. Asymmetric flow field-flow fractionation was used to evaluate the size of APOL1-containing lipoprotein particles in plasma. Transgenic mice that express wild-type or risk variant APOL1 from an albumin promoter were treated to cause kidney injury and evaluated for renal disease and pathology.
In human participants, urine concentrations of APOL1 were correlated with plasma concentrations and reduced kidney function. Risk variant APOL1 was enriched in larger particles. In mice, circulating risk variant APOL1-G1 promoted kidney damage and reduced podocyte density without renal expression of APOL1.
These results suggest that plasma APOL1 is dynamic and contributes to the progression of kidney disease in humans, which may have implications for treatment of APOL1-associated kidney disease and for kidney transplantation.</description><subject>Albumin</subject><subject>Albumins</subject><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apolipoprotein L1 - genetics</subject><subject>Apolipoprotein L1 - metabolism</subject><subject>Apolipoproteins</subject><subject>Apolipoproteins - genetics</subject><subject>Biology and Life Sciences</subject><subject>Chromatography</subject><subject>Chronic kidney failure</subject><subject>Creatinine</subject><subject>Damage</subject><subject>Disease</subject><subject>Disease Models, Animal</subject><subject>Engineering and Technology</subject><subject>Evaluation</subject><subject>Fibroblasts</subject><subject>Fractionation</subject><subject>Genetic diversity</subject><subject>Genetic engineering</subject><subject>Genetic variance</subject><subject>Genotype & phenotype</subject><subject>Genotypes</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Health risks</subject><subject>Humans</subject><subject>Injuries</subject><subject>Kidney - pathology</subject><subject>Kidney diseases</subject><subject>Kidney transplantation</subject><subject>Kidneys</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Liquid chromatography</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Measurement</subject><subject>Medicine and Health Sciences</subject><subject>Methods</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Peptides</subject><subject>Plasma</subject><subject>Polymorphism</subject><subject>Prevention</subject><subject>Proteins</subject><subject>Renal Insufficiency, Chronic - genetics</subject><subject>Renal Insufficiency, Chronic - pathology</subject><subject>Research and Analysis Methods</subject><subject>Risk</subject><subject>Risk factors</subject><subject>Transgenic animals</subject><subject>Transgenic mice</subject><subject>Transplantation</subject><subject>Urine</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptkl2LEzEUhgdR3HX1H4gOCOJNa74mHzdCWfxYKKwX6m3IJJk2NZOMyYzSf2-6nV1aEUISkue857yHU1UvIVhCzOD7XZxSUH45xGCXADFKiXhUXUKB0YIigB-f3C-qZznvAGgwp_RpdYEpYgKJ5rLyP1RyKoz16uvtGtZDiqN1oS5r8Cr3qlY5R-3UaHP9x43b2qu0sakeVBqd9uW1oNupVyHXKpi6j1O2ZTfW5zp29U9ngt0XaDel_fPqSad8ti_m86r6_unjt-svi_Xt55vr1XqhG96MC4NbawAREBFuEBWcs44R0yEKcDGDCW2RoG2nETdAWwsh6SzVlAltNDcQX1Wvj7qDj1nOjcoSMcRBgxBFhbg5EiaqnRyS61Xay6icvHuIaSNngxIqAyETmLQGESjaFiGOOmgJMAZhddD6MGeb2t4abcOYlD8TPf8Jbis38bcUjYCg4UXg3SyQ4q_J5lH2LmvrvQq2tPOubkgYbGhB3_yD_t_dTG1UMeBCF0tefRCVK4YwZ7xpDtTbE2prlR-3OfppdDHkc5AcQZ1izsl2D94gkIdZvC9CHmZRzrNYwl6d9uUh6H748F8JVtuA</recordid><startdate>20221024</startdate><enddate>20221024</enddate><creator>Andrews, Michael</creator><creator>Yoshida, Teruhiko</creator><creator>Henderson, Clark M</creator><creator>Pflaum, Hannah</creator><creator>McGregor, Ayako</creator><creator>Lieberman, Joshua A</creator><creator>de Boer, Ian H</creator><creator>Vaisar, Tomas</creator><creator>Himmelfarb, Jonathan</creator><creator>Kestenbaum, Bryan</creator><creator>Chung, Joon-Yong</creator><creator>Hewitt, Stephen M</creator><creator>Santo, Briana A</creator><creator>Ginley, Brandon</creator><creator>Sarder, Pinaki</creator><creator>Rosenberg, Avi Z</creator><creator>Murakami, Taichi</creator><creator>Kopp, Jeffrey B</creator><creator>Kuklenyik, Zsuzsanna</creator><creator>Hoofnagle, Andrew N</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-1958-909X</orcidid><orcidid>https://orcid.org/0000-0001-9801-7705</orcidid><orcidid>https://orcid.org/0000-0002-2049-7347</orcidid><orcidid>https://orcid.org/0000-0002-6449-0243</orcidid><orcidid>https://orcid.org/0000-0002-7406-6606</orcidid></search><sort><creationdate>20221024</creationdate><title>Variant APOL1 protein in plasma associates with larger particles in humans and mouse models of kidney injury</title><author>Andrews, Michael ; Yoshida, Teruhiko ; Henderson, Clark M ; Pflaum, Hannah ; McGregor, Ayako ; Lieberman, Joshua A ; de Boer, Ian H ; Vaisar, Tomas ; Himmelfarb, Jonathan ; Kestenbaum, Bryan ; Chung, Joon-Yong ; Hewitt, Stephen M ; Santo, Briana A ; Ginley, Brandon ; Sarder, Pinaki ; Rosenberg, Avi Z ; Murakami, Taichi ; Kopp, Jeffrey B ; Kuklenyik, Zsuzsanna ; Hoofnagle, Andrew N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c585t-d3bed0491248d269887f74df2603203346b296bfc28d0cee114fe6c679cdc8d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Albumin</topic><topic>Albumins</topic><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apolipoprotein L1 - genetics</topic><topic>Apolipoprotein L1 - metabolism</topic><topic>Apolipoproteins</topic><topic>Apolipoproteins - genetics</topic><topic>Biology and Life Sciences</topic><topic>Chromatography</topic><topic>Chronic kidney failure</topic><topic>Creatinine</topic><topic>Damage</topic><topic>Disease</topic><topic>Disease Models, Animal</topic><topic>Engineering and Technology</topic><topic>Evaluation</topic><topic>Fibroblasts</topic><topic>Fractionation</topic><topic>Genetic diversity</topic><topic>Genetic engineering</topic><topic>Genetic variance</topic><topic>Genotype & phenotype</topic><topic>Genotypes</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Health risks</topic><topic>Humans</topic><topic>Injuries</topic><topic>Kidney - pathology</topic><topic>Kidney diseases</topic><topic>Kidney transplantation</topic><topic>Kidneys</topic><topic>Kinases</topic><topic>Laboratory animals</topic><topic>Liquid chromatography</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Measurement</topic><topic>Medicine and Health Sciences</topic><topic>Methods</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Peptides</topic><topic>Plasma</topic><topic>Polymorphism</topic><topic>Prevention</topic><topic>Proteins</topic><topic>Renal Insufficiency, Chronic - genetics</topic><topic>Renal Insufficiency, Chronic - pathology</topic><topic>Research and Analysis Methods</topic><topic>Risk</topic><topic>Risk factors</topic><topic>Transgenic animals</topic><topic>Transgenic mice</topic><topic>Transplantation</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Andrews, Michael</creatorcontrib><creatorcontrib>Yoshida, Teruhiko</creatorcontrib><creatorcontrib>Henderson, Clark M</creatorcontrib><creatorcontrib>Pflaum, Hannah</creatorcontrib><creatorcontrib>McGregor, Ayako</creatorcontrib><creatorcontrib>Lieberman, Joshua A</creatorcontrib><creatorcontrib>de Boer, Ian H</creatorcontrib><creatorcontrib>Vaisar, Tomas</creatorcontrib><creatorcontrib>Himmelfarb, Jonathan</creatorcontrib><creatorcontrib>Kestenbaum, Bryan</creatorcontrib><creatorcontrib>Chung, Joon-Yong</creatorcontrib><creatorcontrib>Hewitt, Stephen M</creatorcontrib><creatorcontrib>Santo, Briana A</creatorcontrib><creatorcontrib>Ginley, Brandon</creatorcontrib><creatorcontrib>Sarder, Pinaki</creatorcontrib><creatorcontrib>Rosenberg, Avi Z</creatorcontrib><creatorcontrib>Murakami, Taichi</creatorcontrib><creatorcontrib>Kopp, Jeffrey B</creatorcontrib><creatorcontrib>Kuklenyik, Zsuzsanna</creatorcontrib><creatorcontrib>Hoofnagle, Andrew N</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</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>Andrews, Michael</au><au>Yoshida, Teruhiko</au><au>Henderson, Clark M</au><au>Pflaum, Hannah</au><au>McGregor, Ayako</au><au>Lieberman, Joshua A</au><au>de Boer, Ian H</au><au>Vaisar, Tomas</au><au>Himmelfarb, Jonathan</au><au>Kestenbaum, Bryan</au><au>Chung, Joon-Yong</au><au>Hewitt, Stephen M</au><au>Santo, Briana A</au><au>Ginley, Brandon</au><au>Sarder, Pinaki</au><au>Rosenberg, Avi Z</au><au>Murakami, Taichi</au><au>Kopp, Jeffrey B</au><au>Kuklenyik, Zsuzsanna</au><au>Hoofnagle, Andrew N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Variant APOL1 protein in plasma associates with larger particles in humans and mouse models of kidney injury</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2022-10-24</date><risdate>2022</risdate><volume>17</volume><issue>10</issue><spage>e0276649</spage><epage>e0276649</epage><pages>e0276649-e0276649</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Genetic variants in apolipoprotein L1 (APOL1), a protein that protects humans from infection with African trypanosomes, explain a substantial proportion of the excess risk of chronic kidney disease affecting individuals with sub-Saharan ancestry. The mechanisms by which risk variants damage kidney cells remain incompletely understood. In preclinical models, APOL1 expressed in podocytes can lead to significant kidney injury. In humans, studies in kidney transplant suggest that the effects of APOL1 variants are predominantly driven by donor genotype. Less attention has been paid to a possible role for circulating APOL1 in kidney injury.
Using liquid chromatography-tandem mass spectrometry, the concentrations of APOL1 were measured in plasma and urine from participants in the Seattle Kidney Study. Asymmetric flow field-flow fractionation was used to evaluate the size of APOL1-containing lipoprotein particles in plasma. Transgenic mice that express wild-type or risk variant APOL1 from an albumin promoter were treated to cause kidney injury and evaluated for renal disease and pathology.
In human participants, urine concentrations of APOL1 were correlated with plasma concentrations and reduced kidney function. Risk variant APOL1 was enriched in larger particles. In mice, circulating risk variant APOL1-G1 promoted kidney damage and reduced podocyte density without renal expression of APOL1.
These results suggest that plasma APOL1 is dynamic and contributes to the progression of kidney disease in humans, which may have implications for treatment of APOL1-associated kidney disease and for kidney transplantation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>36279295</pmid><doi>10.1371/journal.pone.0276649</doi><orcidid>https://orcid.org/0000-0003-1958-909X</orcidid><orcidid>https://orcid.org/0000-0001-9801-7705</orcidid><orcidid>https://orcid.org/0000-0002-2049-7347</orcidid><orcidid>https://orcid.org/0000-0002-6449-0243</orcidid><orcidid>https://orcid.org/0000-0002-7406-6606</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2022-10, Vol.17 (10), p.e0276649-e0276649 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_2728052262 |
source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Albumin Albumins Analysis Animal models Animals Apolipoprotein L1 - genetics Apolipoprotein L1 - metabolism Apolipoproteins Apolipoproteins - genetics Biology and Life Sciences Chromatography Chronic kidney failure Creatinine Damage Disease Disease Models, Animal Engineering and Technology Evaluation Fibroblasts Fractionation Genetic diversity Genetic engineering Genetic variance Genotype & phenotype Genotypes Growth factors Health aspects Health risks Humans Injuries Kidney - pathology Kidney diseases Kidney transplantation Kidneys Kinases Laboratory animals Liquid chromatography Mass spectrometry Mass spectroscopy Measurement Medicine and Health Sciences Methods Mice Mice, Transgenic Peptides Plasma Polymorphism Prevention Proteins Renal Insufficiency, Chronic - genetics Renal Insufficiency, Chronic - pathology Research and Analysis Methods Risk Risk factors Transgenic animals Transgenic mice Transplantation Urine |
title | Variant APOL1 protein in plasma associates with larger particles in humans and mouse models of kidney injury |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-18T20%3A51%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Variant%20APOL1%20protein%20in%20plasma%20associates%20with%20larger%20particles%20in%20humans%20and%20mouse%20models%20of%20kidney%20injury&rft.jtitle=PloS%20one&rft.au=Andrews,%20Michael&rft.date=2022-10-24&rft.volume=17&rft.issue=10&rft.spage=e0276649&rft.epage=e0276649&rft.pages=e0276649-e0276649&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0276649&rft_dat=%3Cgale_plos_%3EA723878552%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2728052262&rft_id=info:pmid/36279295&rft_galeid=A723878552&rft_doaj_id=oai_doaj_org_article_1ad117934bd2419bb2282f1e40dd23a2&rfr_iscdi=true |