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
Hauptverfasser: Takeyama, Yasuaki, Uehara, Yuko, Anan, Akira, Morihara, Daisuke, Yokoyama, Keiji, Takata, Kazuhide, Tanaka, Takashi, Irie, Makoto, Iwata, Kaoru, Shakado, Satoshi, Sohda, Tetsuro, Sakisaka, Shotaro
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container_end_page 237
container_issue 4
container_start_page 227
container_title Medical molecular morphology
container_volume 50
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
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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  &lt; 0.05). Hepatic ABCA1 mRNA levels were significantly higher in BDL rats than in control rats ( P  &lt; 0.05). Furthermore, the protein expression level of hepatic ABCA1 was also significantly increased by 200% in BDL rats ( P  &lt; 0.05). In PBC patients, expression of hepatic ABCA1 mRNA was 2.2-fold higher than that in controls ( P  &lt; 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. 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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  &lt; 0.05). Hepatic ABCA1 mRNA levels were significantly higher in BDL rats than in control rats ( P  &lt; 0.05). Furthermore, the protein expression level of hepatic ABCA1 was also significantly increased by 200% in BDL rats ( P  &lt; 0.05). In PBC patients, expression of hepatic ABCA1 mRNA was 2.2-fold higher than that in controls ( P  &lt; 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. 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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 &amp; 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 &amp; 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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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