| Project/Area Number |
17591365
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Hirosaki University |
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Principal Investigator |
HAKAMADA Kenichi Hirosaki University, School of Medicine, Associate Professor, 医学部, 助教授 (30271802)
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| Co-Investigator(Kenkyū-buntansha) |
TOYOKI Yoshikazu Hirosaki University, University Hospital, Assistant, 医学部附属病院, 助手 (70301025)
UMEHARA Yutaka Hirosaki University, University Hospital, Assistant, 医学部附属病院, 助手 (80322931)
SASAKI Mutsuo Hirosaki University, School of Medicine, Professor, 医学部, 教授 (10005077)
池永 照史郎一期 弘前大学, 医学部附属病院, 医員
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | Microarray / liver regeneration / liver failure / organic anion / ATP binding cassette transporter / bilirubin / hyperbilirubinemia |
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| Research Abstract |
Background. Liver damage with hyperbilirubinemia during regeneration of the small liver is the major hurdle to expand indications of adult living donor liver transplantation. We previously reported that decrease in multidrug resistance protein (MRP) 2 and expression of MRP3 during liver regeneration lead to conjugated hyperbilirubinemia after 90% hepatectomy in rats. However, the genetic control of these ATP binding cassette (ABC) transporters under comprehensive review of the gene expression profile during liver regeneration have not been performed yet.
Methods. RNAs were prepared from three rat livers at each time point of 0,24,72, and 168 hr after 90% hepatectomy. Gene expression profile was analyzed by the Rat Genome 230 2.0 array with special references to ABC transporters. Those from rat livers treated with lipopolysaccharide after 70% hepatectomy were also analyzed.
Results. Among 31,042 probes, 1587 reported genes were identified either up-or down-regulated, more than 2-fold. Among 16 ABC transporter genes, MRP2 and OATP1 were significantly down-regulated, while MRP1 and MRP3 tended to be expressed. These genetic changes were confirmed by real-time PCR. These changes were enhanced synergistically by adding lipopolysaccharide during liver regeneration.
Conclusions. Microarray analysis demonstrated not only extensive gene expression profile in the regenerating liver but more specific molecular events related to bilirubin transport at the same time. Changes in expression pattern of ABC transporters, especially down-regulation of MRP2,seem the key event in liver failure during liver regeneration.
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