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Effect of ApoA4 on SERPINA3 mediated by nuclear receptors NR4A1 and NR1D1 in hepatocytes
ApoA4 exerts anti-inflammatory effects, but the mechanism remains unclear. SERPINA3 is a member of the serine proteinase inhibitor gene family, and has been shown to be involved in anti-inflammation and associated with a number of human diseases. In this study, we revealed that ApoA4 stimulates the...
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Published in: | Biochemical and biophysical research communications 2017-05, Vol.487 (2), p.327-332 |
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description | ApoA4 exerts anti-inflammatory effects, but the mechanism remains unclear. SERPINA3 is a member of the serine proteinase inhibitor gene family, and has been shown to be involved in anti-inflammation and associated with a number of human diseases. In this study, we revealed that ApoA4 stimulates the gene expression of SERPINA3 in mouse hepatocytes both in vivo and in vitro, in a dose- and time-dependent manner. The transcriptional response of SERPINA3 to ApoA4 is regulated through the binding of ApoA4 with nuclear receptors NR4A1 and NR1D1 on the SERPINA3 promoter, which was verified with ChIP, Luciferase activity assay and RNA interference-mediated NR4A1 or NR1D1 gene knockdown. These data suggests that ApoA4 transcriptionally induced SERPINA3 expression via NR1D1 and NR4A1. Our findings may throw light on the function of ApoA4 in inflammatory responses and acute-phase reactions, as well as the development of SERPINA3 relative diseases.
•ApoA4 stimulates the expression of SERPINA3 in hepatocytes.•The mechanism works through ApoA4 on the transcription of SERPINA3 via NR4A1 and NR1D1.•ApoA4 may act as an anti-inflammatory response in SERPINA3 relative diseases. |
doi_str_mv | 10.1016/j.bbrc.2017.04.058 |
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•ApoA4 stimulates the expression of SERPINA3 in hepatocytes.•The mechanism works through ApoA4 on the transcription of SERPINA3 via NR4A1 and NR1D1.•ApoA4 may act as an anti-inflammatory response in SERPINA3 relative diseases.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2017.04.058</identifier><identifier>PMID: 28412351</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Animals ; ApoA4 ; Apolipoproteins A - pharmacology ; DISEASES ; GENES ; Hepatocytes - drug effects ; Hepatocytes - metabolism ; Inflammation ; Liver - drug effects ; Liver - metabolism ; LIVER CELLS ; Male ; Metabolic Clearance Rate ; Mice ; Mice, Inbred C57BL ; NR1D1 ; NR4A1 ; Nuclear Receptor Subfamily 1, Group D, Member 1 - metabolism ; Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism ; Organ Specificity - physiology ; RECEPTORS ; SERINE PROTEINASES ; SERPINA3 ; Serpins - metabolism ; TIME DEPENDENCE ; Tissue Distribution ; VISIBLE RADIATION</subject><ispartof>Biochemical and biophysical research communications, 2017-05, Vol.487 (2), p.327-332</ispartof><rights>2017</rights><rights>Copyright © 2017. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c549t-acdeb71ca76f707baa7fa619606871cb35a4f5cf39b592d16981524a741106ad3</citedby><cites>FETCH-LOGICAL-c549t-acdeb71ca76f707baa7fa619606871cb35a4f5cf39b592d16981524a741106ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28412351$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22697030$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yupeng</creatorcontrib><creatorcontrib>He, Jing</creatorcontrib><creatorcontrib>Zhao, Jing</creatorcontrib><creatorcontrib>Xu, Min</creatorcontrib><creatorcontrib>Lou, Danwen</creatorcontrib><creatorcontrib>Tso, Patrick</creatorcontrib><creatorcontrib>Li, Zongfang</creatorcontrib><creatorcontrib>Li, Xiaoming</creatorcontrib><title>Effect of ApoA4 on SERPINA3 mediated by nuclear receptors NR4A1 and NR1D1 in hepatocytes</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>ApoA4 exerts anti-inflammatory effects, but the mechanism remains unclear. SERPINA3 is a member of the serine proteinase inhibitor gene family, and has been shown to be involved in anti-inflammation and associated with a number of human diseases. In this study, we revealed that ApoA4 stimulates the gene expression of SERPINA3 in mouse hepatocytes both in vivo and in vitro, in a dose- and time-dependent manner. The transcriptional response of SERPINA3 to ApoA4 is regulated through the binding of ApoA4 with nuclear receptors NR4A1 and NR1D1 on the SERPINA3 promoter, which was verified with ChIP, Luciferase activity assay and RNA interference-mediated NR4A1 or NR1D1 gene knockdown. These data suggests that ApoA4 transcriptionally induced SERPINA3 expression via NR1D1 and NR4A1. Our findings may throw light on the function of ApoA4 in inflammatory responses and acute-phase reactions, as well as the development of SERPINA3 relative diseases.
•ApoA4 stimulates the expression of SERPINA3 in hepatocytes.•The mechanism works through ApoA4 on the transcription of SERPINA3 via NR4A1 and NR1D1.•ApoA4 may act as an anti-inflammatory response in SERPINA3 relative diseases.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Animals</subject><subject>ApoA4</subject><subject>Apolipoproteins A - pharmacology</subject><subject>DISEASES</subject><subject>GENES</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - metabolism</subject><subject>Inflammation</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>LIVER CELLS</subject><subject>Male</subject><subject>Metabolic Clearance Rate</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>NR1D1</subject><subject>NR4A1</subject><subject>Nuclear Receptor Subfamily 1, Group D, Member 1 - metabolism</subject><subject>Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism</subject><subject>Organ Specificity - physiology</subject><subject>RECEPTORS</subject><subject>SERINE PROTEINASES</subject><subject>SERPINA3</subject><subject>Serpins - metabolism</subject><subject>TIME DEPENDENCE</subject><subject>Tissue Distribution</subject><subject>VISIBLE RADIATION</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp9kVGL1DAUhYso7rj6B3yQgC--tN6bJmkDIpR11IVllVVh30Kapk6GmaYmmYX596bMuuiLTzfcnHtycr-ieIlQIaB4u636PpiKAjYVsAp4-6hYIUgoKQJ7XKwAQJRU4u1Z8SzGLQAiE_JpcUZbhrTmuCpu1-NoTSJ-JN3sO0b8RL6tb75eXnc12dvB6WQH0h_JdDA7qwMJ1tg5-RDJ9Q3rkOhpyCf8gMRNZGNnnbw5JhufF09GvYv2xX09L358XH-_-Fxeffl0edFdlYYzmUptBts3aHQjxgaaXutm1AKlANHmdl9zzUZuxlr2XNIBhWyRU6YbhghCD_V58f7kOx_6nNfYKQW9U3Nwex2Oymun_r2Z3Eb99HeKSy4ksGzw-mTgY3IqGpes2Rg_TXktilIhG6ghq97cPxP8r4ONSe1dNHa305P1h6iwbVvJm1qILKUnqQk-xmDHhzAIagGntmoBpxZwCpjK4PLQq7-_8TDyh1QWvDsJbF7mnbNhiWonkxGFJeng3f_8fwO0G6d3</recordid><startdate>20170527</startdate><enddate>20170527</enddate><creator>Zhang, Yupeng</creator><creator>He, Jing</creator><creator>Zhao, Jing</creator><creator>Xu, Min</creator><creator>Lou, Danwen</creator><creator>Tso, Patrick</creator><creator>Li, Zongfang</creator><creator>Li, Xiaoming</creator><general>Elsevier Inc</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>7X8</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>20170527</creationdate><title>Effect of ApoA4 on SERPINA3 mediated by nuclear receptors NR4A1 and NR1D1 in hepatocytes</title><author>Zhang, Yupeng ; He, Jing ; Zhao, Jing ; Xu, Min ; Lou, Danwen ; Tso, Patrick ; Li, Zongfang ; Li, Xiaoming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c549t-acdeb71ca76f707baa7fa619606871cb35a4f5cf39b592d16981524a741106ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Animals</topic><topic>ApoA4</topic><topic>Apolipoproteins A - pharmacology</topic><topic>DISEASES</topic><topic>GENES</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - metabolism</topic><topic>Inflammation</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>LIVER CELLS</topic><topic>Male</topic><topic>Metabolic Clearance Rate</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>NR1D1</topic><topic>NR4A1</topic><topic>Nuclear Receptor Subfamily 1, Group D, Member 1 - metabolism</topic><topic>Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism</topic><topic>Organ Specificity - physiology</topic><topic>RECEPTORS</topic><topic>SERINE PROTEINASES</topic><topic>SERPINA3</topic><topic>Serpins - metabolism</topic><topic>TIME DEPENDENCE</topic><topic>Tissue Distribution</topic><topic>VISIBLE RADIATION</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yupeng</creatorcontrib><creatorcontrib>He, Jing</creatorcontrib><creatorcontrib>Zhao, Jing</creatorcontrib><creatorcontrib>Xu, Min</creatorcontrib><creatorcontrib>Lou, Danwen</creatorcontrib><creatorcontrib>Tso, Patrick</creatorcontrib><creatorcontrib>Li, Zongfang</creatorcontrib><creatorcontrib>Li, Xiaoming</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yupeng</au><au>He, Jing</au><au>Zhao, Jing</au><au>Xu, Min</au><au>Lou, Danwen</au><au>Tso, Patrick</au><au>Li, Zongfang</au><au>Li, Xiaoming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of ApoA4 on SERPINA3 mediated by nuclear receptors NR4A1 and NR1D1 in hepatocytes</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2017-05-27</date><risdate>2017</risdate><volume>487</volume><issue>2</issue><spage>327</spage><epage>332</epage><pages>327-332</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>ApoA4 exerts anti-inflammatory effects, but the mechanism remains unclear. SERPINA3 is a member of the serine proteinase inhibitor gene family, and has been shown to be involved in anti-inflammation and associated with a number of human diseases. In this study, we revealed that ApoA4 stimulates the gene expression of SERPINA3 in mouse hepatocytes both in vivo and in vitro, in a dose- and time-dependent manner. The transcriptional response of SERPINA3 to ApoA4 is regulated through the binding of ApoA4 with nuclear receptors NR4A1 and NR1D1 on the SERPINA3 promoter, which was verified with ChIP, Luciferase activity assay and RNA interference-mediated NR4A1 or NR1D1 gene knockdown. These data suggests that ApoA4 transcriptionally induced SERPINA3 expression via NR1D1 and NR4A1. Our findings may throw light on the function of ApoA4 in inflammatory responses and acute-phase reactions, as well as the development of SERPINA3 relative diseases.
•ApoA4 stimulates the expression of SERPINA3 in hepatocytes.•The mechanism works through ApoA4 on the transcription of SERPINA3 via NR4A1 and NR1D1.•ApoA4 may act as an anti-inflammatory response in SERPINA3 relative diseases.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28412351</pmid><doi>10.1016/j.bbrc.2017.04.058</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 60 APPLIED LIFE SCIENCES Animals ApoA4 Apolipoproteins A - pharmacology DISEASES GENES Hepatocytes - drug effects Hepatocytes - metabolism Inflammation Liver - drug effects Liver - metabolism LIVER CELLS Male Metabolic Clearance Rate Mice Mice, Inbred C57BL NR1D1 NR4A1 Nuclear Receptor Subfamily 1, Group D, Member 1 - metabolism Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism Organ Specificity - physiology RECEPTORS SERINE PROTEINASES SERPINA3 Serpins - metabolism TIME DEPENDENCE Tissue Distribution VISIBLE RADIATION |
title | Effect of ApoA4 on SERPINA3 mediated by nuclear receptors NR4A1 and NR1D1 in hepatocytes |
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