Increased hepatic ABCA1 transporter is associated with hypercholesterolemia in a cholestatic rat model and primary biliary cholangitis patients
Hepatic ATP-binding cassette A1 (ABCA1) transporter is the modulator of intrahepatic cholesterol levels via the efflux of cholesterol into plasma. This study aimed to determine the expression of hepatic ABCA1 levels in a cholestatic rat model and patients with primary biliary cholangitis (PBC). A ch...
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Veröffentlicht in: | Medical molecular morphology 2017-12, Vol.50 (4), p.227-237 |
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creator | Takeyama, Yasuaki Uehara, Yuko Anan, Akira Morihara, Daisuke Yokoyama, Keiji Takata, Kazuhide Tanaka, Takashi Irie, Makoto Iwata, Kaoru Shakado, Satoshi Sohda, Tetsuro Sakisaka, Shotaro |
description | Hepatic ATP-binding cassette A1 (ABCA1) transporter is the modulator of intrahepatic cholesterol levels via the efflux of cholesterol into plasma. This study aimed to determine the expression of hepatic ABCA1 levels in a cholestatic rat model and patients with primary biliary cholangitis (PBC). A cholesterol efflux study was conducted with
Abca1
knock down using siRNA in WIF9 cells. Cholesterol levels in the ABCA1 siRNA cells in the medium were significantly decreased compared with those in controls (
P
|
doi_str_mv | 10.1007/s00795-017-0166-7 |
format | Article |
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Abca1
knock down using siRNA in WIF9 cells. Cholesterol levels in the ABCA1 siRNA cells in the medium were significantly decreased compared with those in controls (
P
< 0.05). Hepatic ABCA1 mRNA levels were significantly higher in BDL rats than in control rats (
P
< 0.05). Furthermore, the protein expression level of hepatic ABCA1 was also significantly increased by 200% in BDL rats (
P
< 0.05). In PBC patients, expression of hepatic ABCA1 mRNA was 2.2-fold higher than that in controls (
P
< 0.05). The level of hepatic liver X receptor (LXR)β mRNA was correlated with ABCA1 mRNA levels in PBC patients. The expression of hepatic ABCA1 transporter was upregulated in both the cholestatic rat model and PBC patients. Upregulated hepatic ABCA1 may lead to efflux of cholesterol into plasma, thus explaining the mechanism of cholestasis leading to hypercholesterolemia.</description><identifier>ISSN: 1860-1480</identifier><identifier>EISSN: 1860-1499</identifier><identifier>DOI: 10.1007/s00795-017-0166-7</identifier><identifier>PMID: 28660384</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>ABCA1 protein ; Anatomy ; Animals ; ATP Binding Cassette Transporter 1 - antagonists & inhibitors ; ATP Binding Cassette Transporter 1 - genetics ; ATP Binding Cassette Transporter 1 - metabolism ; ATP-binding protein ; Bile ; Biological Transport ; Cell Line, Tumor ; Cholangitis ; Cholestasis ; Cholestasis, Intrahepatic - genetics ; Cholestasis, Intrahepatic - metabolism ; Cholestasis, Intrahepatic - pathology ; Cholesterol ; Cholesterol - metabolism ; Disease Models, Animal ; Gene expression ; Gene Expression Regulation ; Hepatocytes - metabolism ; Hepatocytes - pathology ; Humans ; Hypercholesterolemia ; Hypercholesterolemia - genetics ; Hypercholesterolemia - metabolism ; Hypercholesterolemia - pathology ; Liver ; Liver - metabolism ; Liver - pathology ; Liver Cirrhosis, Biliary - genetics ; Liver Cirrhosis, Biliary - metabolism ; Liver Cirrhosis, Biliary - pathology ; Liver X receptors ; Liver X Receptors - genetics ; Liver X Receptors - metabolism ; Male ; Medicine ; Medicine & Public Health ; Molecular Medicine ; mRNA ; Original Paper ; Pathology ; Rats ; Rats, Wistar ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; Rodents ; Signal Transduction ; siRNA</subject><ispartof>Medical molecular morphology, 2017-12, Vol.50 (4), p.227-237</ispartof><rights>The Japanese Society for Clinical Molecular Morphology 2017</rights><rights>Medical Molecular Morphology is a copyright of Springer, (2017). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-c82910c3c484cb9da4fd8d3e12a3561f185cf9ee26c862e3760e33ac4ee26f73</citedby><cites>FETCH-LOGICAL-c396t-c82910c3c484cb9da4fd8d3e12a3561f185cf9ee26c862e3760e33ac4ee26f73</cites><orcidid>0000-0001-7919-4407</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00795-017-0166-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00795-017-0166-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28660384$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takeyama, Yasuaki</creatorcontrib><creatorcontrib>Uehara, Yuko</creatorcontrib><creatorcontrib>Anan, Akira</creatorcontrib><creatorcontrib>Morihara, Daisuke</creatorcontrib><creatorcontrib>Yokoyama, Keiji</creatorcontrib><creatorcontrib>Takata, Kazuhide</creatorcontrib><creatorcontrib>Tanaka, Takashi</creatorcontrib><creatorcontrib>Irie, Makoto</creatorcontrib><creatorcontrib>Iwata, Kaoru</creatorcontrib><creatorcontrib>Shakado, Satoshi</creatorcontrib><creatorcontrib>Sohda, Tetsuro</creatorcontrib><creatorcontrib>Sakisaka, Shotaro</creatorcontrib><title>Increased hepatic ABCA1 transporter is associated with hypercholesterolemia in a cholestatic rat model and primary biliary cholangitis patients</title><title>Medical molecular morphology</title><addtitle>Med Mol Morphol</addtitle><addtitle>Med Mol Morphol</addtitle><description>Hepatic ATP-binding cassette A1 (ABCA1) transporter is the modulator of intrahepatic cholesterol levels via the efflux of cholesterol into plasma. This study aimed to determine the expression of hepatic ABCA1 levels in a cholestatic rat model and patients with primary biliary cholangitis (PBC). A cholesterol efflux study was conducted with
Abca1
knock down using siRNA in WIF9 cells. Cholesterol levels in the ABCA1 siRNA cells in the medium were significantly decreased compared with those in controls (
P
< 0.05). Hepatic ABCA1 mRNA levels were significantly higher in BDL rats than in control rats (
P
< 0.05). Furthermore, the protein expression level of hepatic ABCA1 was also significantly increased by 200% in BDL rats (
P
< 0.05). In PBC patients, expression of hepatic ABCA1 mRNA was 2.2-fold higher than that in controls (
P
< 0.05). The level of hepatic liver X receptor (LXR)β mRNA was correlated with ABCA1 mRNA levels in PBC patients. The expression of hepatic ABCA1 transporter was upregulated in both the cholestatic rat model and PBC patients. Upregulated hepatic ABCA1 may lead to efflux of cholesterol into plasma, thus explaining the mechanism of cholestasis leading to hypercholesterolemia.</description><subject>ABCA1 protein</subject><subject>Anatomy</subject><subject>Animals</subject><subject>ATP Binding Cassette Transporter 1 - antagonists & inhibitors</subject><subject>ATP Binding Cassette Transporter 1 - genetics</subject><subject>ATP Binding Cassette Transporter 1 - metabolism</subject><subject>ATP-binding protein</subject><subject>Bile</subject><subject>Biological Transport</subject><subject>Cell Line, Tumor</subject><subject>Cholangitis</subject><subject>Cholestasis</subject><subject>Cholestasis, Intrahepatic - genetics</subject><subject>Cholestasis, Intrahepatic - metabolism</subject><subject>Cholestasis, Intrahepatic - pathology</subject><subject>Cholesterol</subject><subject>Cholesterol - metabolism</subject><subject>Disease Models, Animal</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Hepatocytes - metabolism</subject><subject>Hepatocytes - pathology</subject><subject>Humans</subject><subject>Hypercholesterolemia</subject><subject>Hypercholesterolemia - genetics</subject><subject>Hypercholesterolemia - metabolism</subject><subject>Hypercholesterolemia - pathology</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver Cirrhosis, Biliary - genetics</subject><subject>Liver Cirrhosis, Biliary - metabolism</subject><subject>Liver Cirrhosis, Biliary - pathology</subject><subject>Liver X receptors</subject><subject>Liver X Receptors - genetics</subject><subject>Liver X Receptors - metabolism</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular Medicine</subject><subject>mRNA</subject><subject>Original Paper</subject><subject>Pathology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>siRNA</subject><issn>1860-1480</issn><issn>1860-1499</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kclKBDEQhoMo7g_gRQJevLRm6U6nj-PgBoIX7yGTrnYivZlkEJ_CV7baGUUED0mF5Ks_VfUTcsLZBWesvIy4VUXGeIlLqazcIvtcK5bxvKq2f86a7ZGDGF8Yk6USxS7ZE1opJnW-Tz7uexfARqjpEkabvKOzq_mM0xRsH8chJAjUR2pjHJy3Cbk3n5Z0-T5CcMuhhYgEhs5b6ntq6ebySyrYRLuhhpbavqZj8J0N73ThWz_FibT9s0-oP30NfYpHZKexbYTjTTwkTzfXT_O77OHx9n4-e8icrFTKnBYVZ066XOduUdU2b2pdS-DCykLxhuvCNRWAUE4rAdg3Aymty6erppSH5HwtO4bhdYXlms5HBy3WA8MqGl7h2HCIokD07A_6MqxCj8UhpQQXhWCTIF9TLgwxBmjMplvDmZnMMmuzDJplJrPMlHO6UV4tOqh_Mr7dQUCsgYhP_TOEX1__q_oJrlCh7A</recordid><startdate>20171201</startdate><enddate>20171201</enddate><creator>Takeyama, Yasuaki</creator><creator>Uehara, Yuko</creator><creator>Anan, Akira</creator><creator>Morihara, Daisuke</creator><creator>Yokoyama, Keiji</creator><creator>Takata, Kazuhide</creator><creator>Tanaka, Takashi</creator><creator>Irie, Makoto</creator><creator>Iwata, Kaoru</creator><creator>Shakado, Satoshi</creator><creator>Sohda, Tetsuro</creator><creator>Sakisaka, Shotaro</creator><general>Springer Japan</general><general>Springer Nature B.V</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>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7919-4407</orcidid></search><sort><creationdate>20171201</creationdate><title>Increased hepatic ABCA1 transporter is associated with hypercholesterolemia in a cholestatic rat model and primary biliary cholangitis patients</title><author>Takeyama, Yasuaki ; Uehara, Yuko ; Anan, Akira ; Morihara, Daisuke ; Yokoyama, Keiji ; Takata, Kazuhide ; Tanaka, Takashi ; Irie, Makoto ; Iwata, Kaoru ; Shakado, Satoshi ; Sohda, Tetsuro ; Sakisaka, Shotaro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-c82910c3c484cb9da4fd8d3e12a3561f185cf9ee26c862e3760e33ac4ee26f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>ABCA1 protein</topic><topic>Anatomy</topic><topic>Animals</topic><topic>ATP Binding Cassette Transporter 1 - antagonists & inhibitors</topic><topic>ATP Binding Cassette Transporter 1 - genetics</topic><topic>ATP Binding Cassette Transporter 1 - metabolism</topic><topic>ATP-binding protein</topic><topic>Bile</topic><topic>Biological Transport</topic><topic>Cell Line, Tumor</topic><topic>Cholangitis</topic><topic>Cholestasis</topic><topic>Cholestasis, Intrahepatic - genetics</topic><topic>Cholestasis, Intrahepatic - metabolism</topic><topic>Cholestasis, Intrahepatic - pathology</topic><topic>Cholesterol</topic><topic>Cholesterol - metabolism</topic><topic>Disease Models, Animal</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Hepatocytes - metabolism</topic><topic>Hepatocytes - pathology</topic><topic>Humans</topic><topic>Hypercholesterolemia</topic><topic>Hypercholesterolemia - genetics</topic><topic>Hypercholesterolemia - metabolism</topic><topic>Hypercholesterolemia - pathology</topic><topic>Liver</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver Cirrhosis, Biliary - genetics</topic><topic>Liver Cirrhosis, Biliary - metabolism</topic><topic>Liver Cirrhosis, Biliary - pathology</topic><topic>Liver X receptors</topic><topic>Liver X Receptors - genetics</topic><topic>Liver X Receptors - metabolism</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular Medicine</topic><topic>mRNA</topic><topic>Original Paper</topic><topic>Pathology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>siRNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takeyama, Yasuaki</creatorcontrib><creatorcontrib>Uehara, Yuko</creatorcontrib><creatorcontrib>Anan, Akira</creatorcontrib><creatorcontrib>Morihara, Daisuke</creatorcontrib><creatorcontrib>Yokoyama, Keiji</creatorcontrib><creatorcontrib>Takata, Kazuhide</creatorcontrib><creatorcontrib>Tanaka, Takashi</creatorcontrib><creatorcontrib>Irie, Makoto</creatorcontrib><creatorcontrib>Iwata, Kaoru</creatorcontrib><creatorcontrib>Shakado, Satoshi</creatorcontrib><creatorcontrib>Sohda, Tetsuro</creatorcontrib><creatorcontrib>Sakisaka, Shotaro</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>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Medical molecular morphology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takeyama, Yasuaki</au><au>Uehara, Yuko</au><au>Anan, Akira</au><au>Morihara, Daisuke</au><au>Yokoyama, Keiji</au><au>Takata, Kazuhide</au><au>Tanaka, Takashi</au><au>Irie, Makoto</au><au>Iwata, Kaoru</au><au>Shakado, Satoshi</au><au>Sohda, Tetsuro</au><au>Sakisaka, Shotaro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased hepatic ABCA1 transporter is associated with hypercholesterolemia in a cholestatic rat model and primary biliary cholangitis patients</atitle><jtitle>Medical molecular morphology</jtitle><stitle>Med Mol Morphol</stitle><addtitle>Med Mol Morphol</addtitle><date>2017-12-01</date><risdate>2017</risdate><volume>50</volume><issue>4</issue><spage>227</spage><epage>237</epage><pages>227-237</pages><issn>1860-1480</issn><eissn>1860-1499</eissn><abstract>Hepatic ATP-binding cassette A1 (ABCA1) transporter is the modulator of intrahepatic cholesterol levels via the efflux of cholesterol into plasma. This study aimed to determine the expression of hepatic ABCA1 levels in a cholestatic rat model and patients with primary biliary cholangitis (PBC). A cholesterol efflux study was conducted with
Abca1
knock down using siRNA in WIF9 cells. Cholesterol levels in the ABCA1 siRNA cells in the medium were significantly decreased compared with those in controls (
P
< 0.05). Hepatic ABCA1 mRNA levels were significantly higher in BDL rats than in control rats (
P
< 0.05). Furthermore, the protein expression level of hepatic ABCA1 was also significantly increased by 200% in BDL rats (
P
< 0.05). In PBC patients, expression of hepatic ABCA1 mRNA was 2.2-fold higher than that in controls (
P
< 0.05). The level of hepatic liver X receptor (LXR)β mRNA was correlated with ABCA1 mRNA levels in PBC patients. The expression of hepatic ABCA1 transporter was upregulated in both the cholestatic rat model and PBC patients. Upregulated hepatic ABCA1 may lead to efflux of cholesterol into plasma, thus explaining the mechanism of cholestasis leading to hypercholesterolemia.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>28660384</pmid><doi>10.1007/s00795-017-0166-7</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7919-4407</orcidid></addata></record> |
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subjects | ABCA1 protein Anatomy Animals ATP Binding Cassette Transporter 1 - antagonists & inhibitors ATP Binding Cassette Transporter 1 - genetics ATP Binding Cassette Transporter 1 - metabolism ATP-binding protein Bile Biological Transport Cell Line, Tumor Cholangitis Cholestasis Cholestasis, Intrahepatic - genetics Cholestasis, Intrahepatic - metabolism Cholestasis, Intrahepatic - pathology Cholesterol Cholesterol - metabolism Disease Models, Animal Gene expression Gene Expression Regulation Hepatocytes - metabolism Hepatocytes - pathology Humans Hypercholesterolemia Hypercholesterolemia - genetics Hypercholesterolemia - metabolism Hypercholesterolemia - pathology Liver Liver - metabolism Liver - pathology Liver Cirrhosis, Biliary - genetics Liver Cirrhosis, Biliary - metabolism Liver Cirrhosis, Biliary - pathology Liver X receptors Liver X Receptors - genetics Liver X Receptors - metabolism Male Medicine Medicine & Public Health Molecular Medicine mRNA Original Paper Pathology Rats Rats, Wistar RNA, Messenger - genetics RNA, Messenger - metabolism RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Rodents Signal Transduction siRNA |
title | Increased hepatic ABCA1 transporter is associated with hypercholesterolemia in a cholestatic rat model and primary biliary cholangitis patients |
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