https://scholars.lib.ntu.edu.tw/handle/123456789/537046
標題: | Expression of hepatocyte transporters and nuclear receptors in children with early and late-stage biliary atresia | 作者: | HUEY-LING CHEN Liu Y.-J. Chen H.-L. Wu S.-H. YEN-HSUAN NI MING-CHIH HO HONG-SHIEE LAI WEN-MING HSU HONG-YUAN HSU Tseng H.-C. YUNG-MING JENG MEI-HWEI CHANG |
公開日期: | 2008 | 卷: | 63 | 期: | 6 | 起(迄)頁: | 667-673 | 來源出版物: | Pediatric Research | 摘要: | To investigate how the liver adapts to chronic obstructive cholestasis, liver samples from infants with early- and late-stage cholestasis were analyzed for changes in the levels of hepatocyte transporters and nuclear receptors. At early-stage cholestasis, most canalicular transporters and sinusoidal uptake transporters were downregulated, including bile salt export pump (BSEP, ABCB11), multidrug resistant protein 3 (MDR3, ABCB4), multidrug-resistant associated protein 2 (MRP2, ABCC2), sodium-dependent taurocholate cotransporting polypeptide (NTCP, SLC10A1), organic anion transporter (OATP, SLCO1A2), and nuclear receptor farnesoid X receptor (FXR, NR1H4). At late-stage cholestasis, FXR-BSEP levels returned to normal, MDR3 and MDR1 (ABCB1) were upregulated, and MRP-2 was downregulated. In addition, alternative sinusoidal efflux transporters, organic solute transporter alpha/beta (OSTα/β) and MRP4 were upregulated, and pregnane X receptor (PXR, NR1I2) levels decreased. Cytochrome enzyme P450 7A1 was markedly downregulated at both early and late-stage cholestasis. An analysis of the long-term prognosis of 18 patients revealed lower PXR and constitutive androstane receptor (CAR, NR1I3) levels in the poor prognosis group. In conclusion, at long-term cholestasis, hepatocyte bile efflux was through sinusoidal and canalicular transporters, with FXR-BSEP levels maintained and PXR downregulated. Low PXR and CAR levels were associated with poor prognosis. Copyright ? 2008 International Pediatric Research Foundation, Inc. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-45849103909&doi=10.1203%2fPDR.0b013e318170a6b5&partnerID=40&md5=6b8bd287c29a0c4126bf51f9bcccee3a https://scholars.lib.ntu.edu.tw/handle/123456789/537046 |
ISSN: | 0031-3998 | DOI: | 10.1203/PDR.0b013e318170a6b5 | SDG/關鍵字: | cell nucleus receptor; constitutive androstane receptor; cytochrome P450; farnesoid X receptor; multidrug resistance protein 2; multidrug resistance protein 3; multidrug resistance protein 4; organic anion transporter; organic anion transporter 1; pregnane X receptor; carrier protein; cell receptor; messenger RNA; adult; article; bile acid blood level; bile duct atresia; bile duct obstruction; bilirubin blood level; cell transport; child; cholestasis; clinical article; controlled study; effusion; female; human; human cell; human tissue; infant; liver cell; liver sinusoid; male; preschool child; priority journal; protein expression; upregulation; adaptation; bile; bile duct atresia; chemistry; comparative study; disease course; fluorescence microscopy; genetics; intrahepatic cholestasis; liver; liver transplantation; metabolism; newborn; pathology; pathophysiology; prognosis; Adaptation, Physiological; Bile; Biliary Atresia; Cholestasis, Intrahepatic; Disease Progression; Female; Hepatocytes; Humans; Infant; Infant, Newborn; Liver; Liver Transplantation; Male; Membrane Transport Proteins; Microscopy, Fluorescence; Prognosis; Receptors, Cytoplasmic and Nuclear; RNA, Messenger |
顯示於: | 醫學系 |
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