Genomic integration of ERR?-HNF1ß regulates renal bioenergetics and prevents chronic kidney disease

Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. H...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2018-05, Vol.115 (21), p.E4910
Hauptverfasser: Zhao, Juanjuan, Lupino, Katherine, Wilkins, Benjamin J, Qiu, Chengxiang, Liu, Jian, Omura, Yasuhiro, Allred, Amanda L, McDonald, Caitlin, Susztak, Katalin, Barish, Grant D, Pei, Liming
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue 21
container_start_page E4910
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 115
creator Zhao, Juanjuan
Lupino, Katherine
Wilkins, Benjamin J
Qiu, Chengxiang
Liu, Jian
Omura, Yasuhiro
Allred, Amanda L
McDonald, Caitlin
Susztak, Katalin
Barish, Grant D
Pei, Liming
description Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.
format Article
fullrecord <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_journals_2100879528</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2100879528</sourcerecordid><originalsourceid>FETCH-proquest_journals_21008795283</originalsourceid><addsrcrecordid>eNqNjDsKwkAQQBdRMH7uMGAdmMSoSWUhfioLsZc1GeNqnNWdjeBpPIwXM4UHsHqveLyWCiLMonCaZNhWAWI8C9MkTrqqJ3JBxGySYqCKNbG9mRwMeyqd9sYy2BMsd7t5uNmuos8bHJV1pT1JY6wrOBpLTK4kb3IBzQXcHT2JvUB-dpab29UUTC8ojJAWGqjOSVdCwx_7arRa7heb8O7soybxh4utXbOWQxwhprNsEqfj_6ovZRdIDg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2100879528</pqid></control><display><type>article</type><title>Genomic integration of ERR?-HNF1ß regulates renal bioenergetics and prevents chronic kidney disease</title><source>JSTOR Archive Collection A-Z Listing</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Zhao, Juanjuan ; Lupino, Katherine ; Wilkins, Benjamin J ; Qiu, Chengxiang ; Liu, Jian ; Omura, Yasuhiro ; Allred, Amanda L ; McDonald, Caitlin ; Susztak, Katalin ; Barish, Grant D ; Pei, Liming</creator><creatorcontrib>Zhao, Juanjuan ; Lupino, Katherine ; Wilkins, Benjamin J ; Qiu, Chengxiang ; Liu, Jian ; Omura, Yasuhiro ; Allred, Amanda L ; McDonald, Caitlin ; Susztak, Katalin ; Barish, Grant D ; Pei, Liming</creatorcontrib><description>Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><language>eng</language><publisher>Washington: National Academy of Sciences</publisher><subject>Bioenergetics ; Clonal deletion ; Epithelial cells ; Estrogens ; Gene expression ; Genomics ; Hepatocyte nuclear factor 1 ; Kidney diseases ; Kidneys ; Metabolism ; Mitochondria ; Mitochondrial DNA ; Mutation ; Patients ; Phenotypes ; Reabsorption ; Renal failure ; Renal function ; Transcription</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2018-05, Vol.115 (21), p.E4910</ispartof><rights>Copyright National Academy of Sciences May 22, 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids></links><search><creatorcontrib>Zhao, Juanjuan</creatorcontrib><creatorcontrib>Lupino, Katherine</creatorcontrib><creatorcontrib>Wilkins, Benjamin J</creatorcontrib><creatorcontrib>Qiu, Chengxiang</creatorcontrib><creatorcontrib>Liu, Jian</creatorcontrib><creatorcontrib>Omura, Yasuhiro</creatorcontrib><creatorcontrib>Allred, Amanda L</creatorcontrib><creatorcontrib>McDonald, Caitlin</creatorcontrib><creatorcontrib>Susztak, Katalin</creatorcontrib><creatorcontrib>Barish, Grant D</creatorcontrib><creatorcontrib>Pei, Liming</creatorcontrib><title>Genomic integration of ERR?-HNF1ß regulates renal bioenergetics and prevents chronic kidney disease</title><title>Proceedings of the National Academy of Sciences - PNAS</title><description>Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.</description><subject>Bioenergetics</subject><subject>Clonal deletion</subject><subject>Epithelial cells</subject><subject>Estrogens</subject><subject>Gene expression</subject><subject>Genomics</subject><subject>Hepatocyte nuclear factor 1</subject><subject>Kidney diseases</subject><subject>Kidneys</subject><subject>Metabolism</subject><subject>Mitochondria</subject><subject>Mitochondrial DNA</subject><subject>Mutation</subject><subject>Patients</subject><subject>Phenotypes</subject><subject>Reabsorption</subject><subject>Renal failure</subject><subject>Renal function</subject><subject>Transcription</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqNjDsKwkAQQBdRMH7uMGAdmMSoSWUhfioLsZc1GeNqnNWdjeBpPIwXM4UHsHqveLyWCiLMonCaZNhWAWI8C9MkTrqqJ3JBxGySYqCKNbG9mRwMeyqd9sYy2BMsd7t5uNmuos8bHJV1pT1JY6wrOBpLTK4kb3IBzQXcHT2JvUB-dpab29UUTC8ojJAWGqjOSVdCwx_7arRa7heb8O7soybxh4utXbOWQxwhprNsEqfj_6ovZRdIDg</recordid><startdate>20180522</startdate><enddate>20180522</enddate><creator>Zhao, Juanjuan</creator><creator>Lupino, Katherine</creator><creator>Wilkins, Benjamin J</creator><creator>Qiu, Chengxiang</creator><creator>Liu, Jian</creator><creator>Omura, Yasuhiro</creator><creator>Allred, Amanda L</creator><creator>McDonald, Caitlin</creator><creator>Susztak, Katalin</creator><creator>Barish, Grant D</creator><creator>Pei, Liming</creator><general>National Academy of Sciences</general><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20180522</creationdate><title>Genomic integration of ERR?-HNF1ß regulates renal bioenergetics and prevents chronic kidney disease</title><author>Zhao, Juanjuan ; Lupino, Katherine ; Wilkins, Benjamin J ; Qiu, Chengxiang ; Liu, Jian ; Omura, Yasuhiro ; Allred, Amanda L ; McDonald, Caitlin ; Susztak, Katalin ; Barish, Grant D ; Pei, Liming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_journals_21008795283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Bioenergetics</topic><topic>Clonal deletion</topic><topic>Epithelial cells</topic><topic>Estrogens</topic><topic>Gene expression</topic><topic>Genomics</topic><topic>Hepatocyte nuclear factor 1</topic><topic>Kidney diseases</topic><topic>Kidneys</topic><topic>Metabolism</topic><topic>Mitochondria</topic><topic>Mitochondrial DNA</topic><topic>Mutation</topic><topic>Patients</topic><topic>Phenotypes</topic><topic>Reabsorption</topic><topic>Renal failure</topic><topic>Renal function</topic><topic>Transcription</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Juanjuan</creatorcontrib><creatorcontrib>Lupino, Katherine</creatorcontrib><creatorcontrib>Wilkins, Benjamin J</creatorcontrib><creatorcontrib>Qiu, Chengxiang</creatorcontrib><creatorcontrib>Liu, Jian</creatorcontrib><creatorcontrib>Omura, Yasuhiro</creatorcontrib><creatorcontrib>Allred, Amanda L</creatorcontrib><creatorcontrib>McDonald, Caitlin</creatorcontrib><creatorcontrib>Susztak, Katalin</creatorcontrib><creatorcontrib>Barish, Grant D</creatorcontrib><creatorcontrib>Pei, Liming</creatorcontrib><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Juanjuan</au><au>Lupino, Katherine</au><au>Wilkins, Benjamin J</au><au>Qiu, Chengxiang</au><au>Liu, Jian</au><au>Omura, Yasuhiro</au><au>Allred, Amanda L</au><au>McDonald, Caitlin</au><au>Susztak, Katalin</au><au>Barish, Grant D</au><au>Pei, Liming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomic integration of ERR?-HNF1ß regulates renal bioenergetics and prevents chronic kidney disease</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><date>2018-05-22</date><risdate>2018</risdate><volume>115</volume><issue>21</issue><spage>E4910</spage><pages>E4910-</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.</abstract><cop>Washington</cop><pub>National Academy of Sciences</pub></addata></record>
fulltext fulltext
identifier ISSN: 0027-8424
ispartof Proceedings of the National Academy of Sciences - PNAS, 2018-05, Vol.115 (21), p.E4910
issn 0027-8424
1091-6490
language eng
recordid cdi_proquest_journals_2100879528
source JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry
subjects Bioenergetics
Clonal deletion
Epithelial cells
Estrogens
Gene expression
Genomics
Hepatocyte nuclear factor 1
Kidney diseases
Kidneys
Metabolism
Mitochondria
Mitochondrial DNA
Mutation
Patients
Phenotypes
Reabsorption
Renal failure
Renal function
Transcription
title Genomic integration of ERR?-HNF1ß regulates renal bioenergetics and prevents chronic kidney disease
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T21%3A14%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genomic%20integration%20of%20ERR?-HNF1%C3%9F%20regulates%20renal%20bioenergetics%20and%20prevents%20chronic%20kidney%20disease&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Zhao,%20Juanjuan&rft.date=2018-05-22&rft.volume=115&rft.issue=21&rft.spage=E4910&rft.pages=E4910-&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/&rft_dat=%3Cproquest%3E2100879528%3C/proquest%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2100879528&rft_id=info:pmid/&rfr_iscdi=true