Splicing Factor SLU7 Prevents Oxidative Stress‐Mediated Hepatocyte Nuclear Factor 4α Degradation, Preserving Hepatic Differentiation and Protecting From Liver Damage
Background and Aims Hepatocellular dedifferentiation is emerging as an important determinant in liver disease progression. Preservation of mature hepatocyte identity relies on a set of key genes, predominantly the transcription factor hepatocyte nuclear factor 4α (HNF4α) but also splicing factors li...
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| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2021-11, Vol.74 (5), p.2791-2807 |
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| creator | Gárate‐Rascón, María Recalde, Miriam Jimenez, Maddalen Elizalde, María Azkona, María Uriarte, Iker Latasa, M. Uxue Urtasun, Raquel Bilbao, Idoia Sangro, Bruno Garcia‐Ruiz, Carmen Fernandez‐Checa, José C. Corrales, Fernando J Esquivel, Argitxu Pineda‐Lucena, Antonio Fernández‐Barrena, Maite G. Ávila, Matías A. Arechederra, María Berasain, Carmen |
| description | Background and Aims
Hepatocellular dedifferentiation is emerging as an important determinant in liver disease progression. Preservation of mature hepatocyte identity relies on a set of key genes, predominantly the transcription factor hepatocyte nuclear factor 4α (HNF4α) but also splicing factors like SLU7. How these factors interact and become dysregulated and the impact of their impairment in driving liver disease are not fully understood.
Approach and Results
Expression of SLU7 and that of the adult and oncofetal isoforms of HNF4α, driven by its promoter 1 (P1) and P2, respectively, was studied in diseased human and mouse livers. Hepatic function and damage response were analyzed in wild‐type and Slu7‐haploinsufficient/heterozygous (Slu7+/−) mice undergoing chronic (CCl4) and acute (acetaminophen) injury. SLU7 expression was restored in CCl4‐injured mice using SLU7‐expressing adeno‐associated viruses (AAV‐SLU7). The hepatocellular SLU7 interactome was characterized by mass spectrometry. Reduced SLU7 expression in human and mouse diseased livers correlated with a switch in HNF4α P1 to P2 usage. This response was reproduced in Slu7+/− mice, which displayed increased sensitivity to chronic and acute liver injury, enhanced oxidative stress, and marked impairment of hepatic functions. AAV‐SLU7 infection prevented liver injury and hepatocellular dedifferentiation. Mechanistically we demonstrate a unique role for SLU7 in the preservation of HNF4α1 protein stability through its capacity to protect the liver against oxidative stress. SLU7 is herein identified as a key component of the stress granule proteome, an essential part of the cell’s antioxidant machinery.
Conclusions
Our results place SLU7 at the highest level of hepatocellular identity control, identifying SLU7 as a link between stress‐protective mechanisms and liver differentiation. These findings emphasize the importance of the preservation of hepatic functions in the protection from liver injury. |
| doi_str_mv | 10.1002/hep.32029 |
| format | Article |
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Hepatocellular dedifferentiation is emerging as an important determinant in liver disease progression. Preservation of mature hepatocyte identity relies on a set of key genes, predominantly the transcription factor hepatocyte nuclear factor 4α (HNF4α) but also splicing factors like SLU7. How these factors interact and become dysregulated and the impact of their impairment in driving liver disease are not fully understood.
Approach and Results
Expression of SLU7 and that of the adult and oncofetal isoforms of HNF4α, driven by its promoter 1 (P1) and P2, respectively, was studied in diseased human and mouse livers. Hepatic function and damage response were analyzed in wild‐type and Slu7‐haploinsufficient/heterozygous (Slu7+/−) mice undergoing chronic (CCl4) and acute (acetaminophen) injury. SLU7 expression was restored in CCl4‐injured mice using SLU7‐expressing adeno‐associated viruses (AAV‐SLU7). The hepatocellular SLU7 interactome was characterized by mass spectrometry. Reduced SLU7 expression in human and mouse diseased livers correlated with a switch in HNF4α P1 to P2 usage. This response was reproduced in Slu7+/− mice, which displayed increased sensitivity to chronic and acute liver injury, enhanced oxidative stress, and marked impairment of hepatic functions. AAV‐SLU7 infection prevented liver injury and hepatocellular dedifferentiation. Mechanistically we demonstrate a unique role for SLU7 in the preservation of HNF4α1 protein stability through its capacity to protect the liver against oxidative stress. SLU7 is herein identified as a key component of the stress granule proteome, an essential part of the cell’s antioxidant machinery.
Conclusions
Our results place SLU7 at the highest level of hepatocellular identity control, identifying SLU7 as a link between stress‐protective mechanisms and liver differentiation. These findings emphasize the importance of the preservation of hepatic functions in the protection from liver injury.</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.32029</identifier><identifier>PMID: 34170569</identifier><language>eng</language><publisher>United States: Wolters Kluwer Health, Inc</publisher><subject>Acetaminophen ; Acetaminophen - administration & dosage ; Acetaminophen - toxicity ; Animals ; Antioxidants ; Carbon tetrachloride ; Carbon Tetrachloride - administration & dosage ; Carbon Tetrachloride - toxicity ; Cell Differentiation - genetics ; Cell Line ; Chemical and Drug Induced Liver Injury - genetics ; Chemical and Drug Induced Liver Injury - pathology ; Disease Models, Animal ; Driving ability ; Hepatocyte Nuclear Factor 4 - genetics ; Hepatocyte Nuclear Factor 4 - metabolism ; Hepatocytes - pathology ; Hepatology ; Humans ; Isoforms ; Liver - cytology ; Liver - drug effects ; Liver - pathology ; Liver diseases ; Male ; Mass spectroscopy ; Mice ; Oxidative stress ; Oxidative Stress - genetics ; Preservation ; Promoter Regions, Genetic ; Proteolysis ; Proteomes ; RNA Splicing Factors - metabolism ; Splicing factors ; Transcriptional Activation</subject><ispartof>Hepatology (Baltimore, Md.), 2021-11, Vol.74 (5), p.2791-2807</ispartof><rights>2021 The Authors. published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.</rights><rights>2021 The Authors. HEPATOLOGY published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (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-c3889-2a1119bb99ac3e3b9f5fdddc358ed9c6b5cf35a93a903abba8725a25b816e2f43</citedby><cites>FETCH-LOGICAL-c3889-2a1119bb99ac3e3b9f5fdddc358ed9c6b5cf35a93a903abba8725a25b816e2f43</cites><orcidid>0000-0001-7075-2476 ; 0000-0001-6570-3557 ; 0000-0002-4830-1924 ; 0000-0003-0375-6236</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhep.32029$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhep.32029$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34170569$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gárate‐Rascón, María</creatorcontrib><creatorcontrib>Recalde, Miriam</creatorcontrib><creatorcontrib>Jimenez, Maddalen</creatorcontrib><creatorcontrib>Elizalde, María</creatorcontrib><creatorcontrib>Azkona, María</creatorcontrib><creatorcontrib>Uriarte, Iker</creatorcontrib><creatorcontrib>Latasa, M. Uxue</creatorcontrib><creatorcontrib>Urtasun, Raquel</creatorcontrib><creatorcontrib>Bilbao, Idoia</creatorcontrib><creatorcontrib>Sangro, Bruno</creatorcontrib><creatorcontrib>Garcia‐Ruiz, Carmen</creatorcontrib><creatorcontrib>Fernandez‐Checa, José C.</creatorcontrib><creatorcontrib>Corrales, Fernando J</creatorcontrib><creatorcontrib>Esquivel, Argitxu</creatorcontrib><creatorcontrib>Pineda‐Lucena, Antonio</creatorcontrib><creatorcontrib>Fernández‐Barrena, Maite G.</creatorcontrib><creatorcontrib>Ávila, Matías A.</creatorcontrib><creatorcontrib>Arechederra, María</creatorcontrib><creatorcontrib>Berasain, Carmen</creatorcontrib><title>Splicing Factor SLU7 Prevents Oxidative Stress‐Mediated Hepatocyte Nuclear Factor 4α Degradation, Preserving Hepatic Differentiation and Protecting From Liver Damage</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>Background and Aims
Hepatocellular dedifferentiation is emerging as an important determinant in liver disease progression. Preservation of mature hepatocyte identity relies on a set of key genes, predominantly the transcription factor hepatocyte nuclear factor 4α (HNF4α) but also splicing factors like SLU7. How these factors interact and become dysregulated and the impact of their impairment in driving liver disease are not fully understood.
Approach and Results
Expression of SLU7 and that of the adult and oncofetal isoforms of HNF4α, driven by its promoter 1 (P1) and P2, respectively, was studied in diseased human and mouse livers. Hepatic function and damage response were analyzed in wild‐type and Slu7‐haploinsufficient/heterozygous (Slu7+/−) mice undergoing chronic (CCl4) and acute (acetaminophen) injury. SLU7 expression was restored in CCl4‐injured mice using SLU7‐expressing adeno‐associated viruses (AAV‐SLU7). The hepatocellular SLU7 interactome was characterized by mass spectrometry. Reduced SLU7 expression in human and mouse diseased livers correlated with a switch in HNF4α P1 to P2 usage. This response was reproduced in Slu7+/− mice, which displayed increased sensitivity to chronic and acute liver injury, enhanced oxidative stress, and marked impairment of hepatic functions. AAV‐SLU7 infection prevented liver injury and hepatocellular dedifferentiation. Mechanistically we demonstrate a unique role for SLU7 in the preservation of HNF4α1 protein stability through its capacity to protect the liver against oxidative stress. SLU7 is herein identified as a key component of the stress granule proteome, an essential part of the cell’s antioxidant machinery.
Conclusions
Our results place SLU7 at the highest level of hepatocellular identity control, identifying SLU7 as a link between stress‐protective mechanisms and liver differentiation. These findings emphasize the importance of the preservation of hepatic functions in the protection from liver injury.</description><subject>Acetaminophen</subject><subject>Acetaminophen - administration & dosage</subject><subject>Acetaminophen - toxicity</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Carbon tetrachloride</subject><subject>Carbon Tetrachloride - administration & dosage</subject><subject>Carbon Tetrachloride - toxicity</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Line</subject><subject>Chemical and Drug Induced Liver Injury - genetics</subject><subject>Chemical and Drug Induced Liver Injury - pathology</subject><subject>Disease Models, Animal</subject><subject>Driving ability</subject><subject>Hepatocyte Nuclear Factor 4 - genetics</subject><subject>Hepatocyte Nuclear Factor 4 - metabolism</subject><subject>Hepatocytes - pathology</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Isoforms</subject><subject>Liver - cytology</subject><subject>Liver - drug effects</subject><subject>Liver - pathology</subject><subject>Liver diseases</subject><subject>Male</subject><subject>Mass spectroscopy</subject><subject>Mice</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - genetics</subject><subject>Preservation</subject><subject>Promoter Regions, Genetic</subject><subject>Proteolysis</subject><subject>Proteomes</subject><subject>RNA Splicing Factors - metabolism</subject><subject>Splicing factors</subject><subject>Transcriptional Activation</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kUtuFDEQhi0EIkNgwQWQJTYg0Ykf7e72EmUSBmkgkYasW9Xu6sFRv2K7B2bHETgGWy7CITgJnpmEBRKr2nz1_aX6CXnO2QlnTJx-xvFECib0AzLjSuSJlIo9JDMmcpZoLvUReeL9DWNMp6J4TI5kynOmMj0jP1Zja43t1_QCTBgcXS2vc3rlcIN98PTyq60h2A3SVXDo_e9v3z9gbSFgTRc4QhjMNiD9OJkWwd070l8_6RzXDna7Q_9m5_PoNruY_ZY1dG6bBl0MsXuGQl9HbAhowv4aN3R0GYMdnUMHa3xKHjXQenx2N4_J9cX5p7NFsrx89_7s7TIxsih0IoBzrqtKazASZaUb1dR1baQqsNYmq5RppAItQTMJVQVFLhQIVRU8Q9Gk8pi8OnhHN9xO6EPZWW-wbaHHYfKlUKnK4mO5iujLf9CbYXJ9vC5ShSyETjMdqdcHyrjBe4dNOTrbgduWnJW7-spYX7mvL7Iv7oxT1WH9l7zvKwKnB-CLbXH7f1O5OL86KP8AH6KoFw</recordid><startdate>202111</startdate><enddate>202111</enddate><creator>Gárate‐Rascón, María</creator><creator>Recalde, Miriam</creator><creator>Jimenez, Maddalen</creator><creator>Elizalde, María</creator><creator>Azkona, María</creator><creator>Uriarte, Iker</creator><creator>Latasa, M. Uxue</creator><creator>Urtasun, Raquel</creator><creator>Bilbao, Idoia</creator><creator>Sangro, Bruno</creator><creator>Garcia‐Ruiz, Carmen</creator><creator>Fernandez‐Checa, José C.</creator><creator>Corrales, Fernando J</creator><creator>Esquivel, Argitxu</creator><creator>Pineda‐Lucena, Antonio</creator><creator>Fernández‐Barrena, Maite G.</creator><creator>Ávila, Matías A.</creator><creator>Arechederra, María</creator><creator>Berasain, Carmen</creator><general>Wolters Kluwer Health, Inc</general><scope>24P</scope><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>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7075-2476</orcidid><orcidid>https://orcid.org/0000-0001-6570-3557</orcidid><orcidid>https://orcid.org/0000-0002-4830-1924</orcidid><orcidid>https://orcid.org/0000-0003-0375-6236</orcidid></search><sort><creationdate>202111</creationdate><title>Splicing Factor SLU7 Prevents Oxidative Stress‐Mediated Hepatocyte Nuclear Factor 4α Degradation, Preserving Hepatic Differentiation and Protecting From Liver Damage</title><author>Gárate‐Rascón, María ; Recalde, Miriam ; Jimenez, Maddalen ; Elizalde, María ; Azkona, María ; Uriarte, Iker ; Latasa, M. Uxue ; Urtasun, Raquel ; Bilbao, Idoia ; Sangro, Bruno ; Garcia‐Ruiz, Carmen ; Fernandez‐Checa, José C. ; Corrales, Fernando J ; Esquivel, Argitxu ; Pineda‐Lucena, Antonio ; Fernández‐Barrena, Maite G. ; Ávila, Matías A. ; Arechederra, María ; Berasain, Carmen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3889-2a1119bb99ac3e3b9f5fdddc358ed9c6b5cf35a93a903abba8725a25b816e2f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acetaminophen</topic><topic>Acetaminophen - administration & dosage</topic><topic>Acetaminophen - toxicity</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Carbon tetrachloride</topic><topic>Carbon Tetrachloride - administration & dosage</topic><topic>Carbon Tetrachloride - toxicity</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Line</topic><topic>Chemical and Drug Induced Liver Injury - genetics</topic><topic>Chemical and Drug Induced Liver Injury - pathology</topic><topic>Disease Models, Animal</topic><topic>Driving ability</topic><topic>Hepatocyte Nuclear Factor 4 - genetics</topic><topic>Hepatocyte Nuclear Factor 4 - metabolism</topic><topic>Hepatocytes - pathology</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Isoforms</topic><topic>Liver - cytology</topic><topic>Liver - drug effects</topic><topic>Liver - pathology</topic><topic>Liver diseases</topic><topic>Male</topic><topic>Mass spectroscopy</topic><topic>Mice</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - genetics</topic><topic>Preservation</topic><topic>Promoter Regions, Genetic</topic><topic>Proteolysis</topic><topic>Proteomes</topic><topic>RNA Splicing Factors - metabolism</topic><topic>Splicing factors</topic><topic>Transcriptional Activation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gárate‐Rascón, María</creatorcontrib><creatorcontrib>Recalde, Miriam</creatorcontrib><creatorcontrib>Jimenez, Maddalen</creatorcontrib><creatorcontrib>Elizalde, María</creatorcontrib><creatorcontrib>Azkona, María</creatorcontrib><creatorcontrib>Uriarte, Iker</creatorcontrib><creatorcontrib>Latasa, M. Uxue</creatorcontrib><creatorcontrib>Urtasun, Raquel</creatorcontrib><creatorcontrib>Bilbao, Idoia</creatorcontrib><creatorcontrib>Sangro, Bruno</creatorcontrib><creatorcontrib>Garcia‐Ruiz, Carmen</creatorcontrib><creatorcontrib>Fernandez‐Checa, José C.</creatorcontrib><creatorcontrib>Corrales, Fernando J</creatorcontrib><creatorcontrib>Esquivel, Argitxu</creatorcontrib><creatorcontrib>Pineda‐Lucena, Antonio</creatorcontrib><creatorcontrib>Fernández‐Barrena, Maite G.</creatorcontrib><creatorcontrib>Ávila, Matías A.</creatorcontrib><creatorcontrib>Arechederra, María</creatorcontrib><creatorcontrib>Berasain, Carmen</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gárate‐Rascón, María</au><au>Recalde, Miriam</au><au>Jimenez, Maddalen</au><au>Elizalde, María</au><au>Azkona, María</au><au>Uriarte, Iker</au><au>Latasa, M. Uxue</au><au>Urtasun, Raquel</au><au>Bilbao, Idoia</au><au>Sangro, Bruno</au><au>Garcia‐Ruiz, Carmen</au><au>Fernandez‐Checa, José C.</au><au>Corrales, Fernando J</au><au>Esquivel, Argitxu</au><au>Pineda‐Lucena, Antonio</au><au>Fernández‐Barrena, Maite G.</au><au>Ávila, Matías A.</au><au>Arechederra, María</au><au>Berasain, Carmen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Splicing Factor SLU7 Prevents Oxidative Stress‐Mediated Hepatocyte Nuclear Factor 4α Degradation, Preserving Hepatic Differentiation and Protecting From Liver Damage</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2021-11</date><risdate>2021</risdate><volume>74</volume><issue>5</issue><spage>2791</spage><epage>2807</epage><pages>2791-2807</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><abstract>Background and Aims
Hepatocellular dedifferentiation is emerging as an important determinant in liver disease progression. Preservation of mature hepatocyte identity relies on a set of key genes, predominantly the transcription factor hepatocyte nuclear factor 4α (HNF4α) but also splicing factors like SLU7. How these factors interact and become dysregulated and the impact of their impairment in driving liver disease are not fully understood.
Approach and Results
Expression of SLU7 and that of the adult and oncofetal isoforms of HNF4α, driven by its promoter 1 (P1) and P2, respectively, was studied in diseased human and mouse livers. Hepatic function and damage response were analyzed in wild‐type and Slu7‐haploinsufficient/heterozygous (Slu7+/−) mice undergoing chronic (CCl4) and acute (acetaminophen) injury. SLU7 expression was restored in CCl4‐injured mice using SLU7‐expressing adeno‐associated viruses (AAV‐SLU7). The hepatocellular SLU7 interactome was characterized by mass spectrometry. Reduced SLU7 expression in human and mouse diseased livers correlated with a switch in HNF4α P1 to P2 usage. This response was reproduced in Slu7+/− mice, which displayed increased sensitivity to chronic and acute liver injury, enhanced oxidative stress, and marked impairment of hepatic functions. AAV‐SLU7 infection prevented liver injury and hepatocellular dedifferentiation. Mechanistically we demonstrate a unique role for SLU7 in the preservation of HNF4α1 protein stability through its capacity to protect the liver against oxidative stress. SLU7 is herein identified as a key component of the stress granule proteome, an essential part of the cell’s antioxidant machinery.
Conclusions
Our results place SLU7 at the highest level of hepatocellular identity control, identifying SLU7 as a link between stress‐protective mechanisms and liver differentiation. These findings emphasize the importance of the preservation of hepatic functions in the protection from liver injury.</abstract><cop>United States</cop><pub>Wolters Kluwer Health, Inc</pub><pmid>34170569</pmid><doi>10.1002/hep.32029</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0001-7075-2476</orcidid><orcidid>https://orcid.org/0000-0001-6570-3557</orcidid><orcidid>https://orcid.org/0000-0002-4830-1924</orcidid><orcidid>https://orcid.org/0000-0003-0375-6236</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0270-9139 |
| ispartof | Hepatology (Baltimore, Md.), 2021-11, Vol.74 (5), p.2791-2807 |
| issn | 0270-9139 1527-3350 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2545602715 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Acetaminophen Acetaminophen - administration & dosage Acetaminophen - toxicity Animals Antioxidants Carbon tetrachloride Carbon Tetrachloride - administration & dosage Carbon Tetrachloride - toxicity Cell Differentiation - genetics Cell Line Chemical and Drug Induced Liver Injury - genetics Chemical and Drug Induced Liver Injury - pathology Disease Models, Animal Driving ability Hepatocyte Nuclear Factor 4 - genetics Hepatocyte Nuclear Factor 4 - metabolism Hepatocytes - pathology Hepatology Humans Isoforms Liver - cytology Liver - drug effects Liver - pathology Liver diseases Male Mass spectroscopy Mice Oxidative stress Oxidative Stress - genetics Preservation Promoter Regions, Genetic Proteolysis Proteomes RNA Splicing Factors - metabolism Splicing factors Transcriptional Activation |
| title | Splicing Factor SLU7 Prevents Oxidative Stress‐Mediated Hepatocyte Nuclear Factor 4α Degradation, Preserving Hepatic Differentiation and Protecting From Liver Damage |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T22%3A25%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Splicing%20Factor%20SLU7%20Prevents%20Oxidative%20Stress%E2%80%90Mediated%20Hepatocyte%20Nuclear%20Factor%204%CE%B1%20Degradation,%20Preserving%20Hepatic%20Differentiation%20and%20Protecting%20From%20Liver%20Damage&rft.jtitle=Hepatology%20(Baltimore,%20Md.)&rft.au=G%C3%A1rate%E2%80%90Rasc%C3%B3n,%20Mar%C3%ADa&rft.date=2021-11&rft.volume=74&rft.issue=5&rft.spage=2791&rft.epage=2807&rft.pages=2791-2807&rft.issn=0270-9139&rft.eissn=1527-3350&rft_id=info:doi/10.1002/hep.32029&rft_dat=%3Cproquest_cross%3E2545602715%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2583829469&rft_id=info:pmid/34170569&rfr_iscdi=true |