Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection

Eiji Hinoshita, Ken ichi Taguchi, Akihiko Inokuchi, Takeshi Uchiumi, Naoko Kinukawa, Mitsuo Shimada, Masazumi Tsuneyoshi, Keizo Sugimachi, Michihiko Kuwano

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Abstract

Background/Aims: To understand hepatic injury during the process of hepatitis viral infection, determination of liver-specific functions at molecular levels is critical. Because the transport of endogenous/exogenous toxic substances is an intrinsically important hepatic function, we examined whether expression of the ATP-binding cassette (ABC) transporter gene was affected in patients with hepatitis viral infection. Methods: To determine which ABC transporter was expressed differently in patients with hepatic viral infection, we assayed the expression of MDR1, MDR3, MRP1, MRP2, and MRP3 in non-cancerous regions in the liver of 42 patients with hepatic tumors using both quantitative RT-PCR and immunological staining analysis, and compared the hepatic expression levels between patients with hepatitis viral infection and non-infected controls. Results: Of the five ABC transporter genes studied, the mRNAs of MRP2 and MRP3 were highly expressed in the human liver. There was a significant reduction in MRP2 expression to 29% in the virus-infected liver. Treatment of hepatic cells with inflammatory cytokines resulted in decreased mRNA levels of MRP2 and decreased MRP2 promoter activity. Conclusions: The down-regulation of MRP2 might induce a failure in the transport of various genotoxic substances in the liver with hepatitis virus infection.

Original languageEnglish
Pages (from-to)765-773
Number of pages9
JournalJournal of Hepatology
Volume35
Issue number6
DOIs
Publication statusPublished - Dec 1 2001

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ATP-Binding Cassette Transporters
Virus Diseases
Hepacivirus
Liver
Hepatitis
Hepatitis Viruses
Messenger RNA
Poisons
Genes
Hepatocytes
Down-Regulation
Staining and Labeling
Cytokines
Viruses
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Hepatology

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Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection. / Hinoshita, Eiji; Taguchi, Ken ichi; Inokuchi, Akihiko; Uchiumi, Takeshi; Kinukawa, Naoko; Shimada, Mitsuo; Tsuneyoshi, Masazumi; Sugimachi, Keizo; Kuwano, Michihiko.

In: Journal of Hepatology, Vol. 35, No. 6, 01.12.2001, p. 765-773.

Research output: Contribution to journalArticle

Hinoshita, E, Taguchi, KI, Inokuchi, A, Uchiumi, T, Kinukawa, N, Shimada, M, Tsuneyoshi, M, Sugimachi, K & Kuwano, M 2001, 'Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection', Journal of Hepatology, vol. 35, no. 6, pp. 765-773. https://doi.org/10.1016/S0168-8278(01)00216-1
Hinoshita, Eiji ; Taguchi, Ken ichi ; Inokuchi, Akihiko ; Uchiumi, Takeshi ; Kinukawa, Naoko ; Shimada, Mitsuo ; Tsuneyoshi, Masazumi ; Sugimachi, Keizo ; Kuwano, Michihiko. / Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection. In: Journal of Hepatology. 2001 ; Vol. 35, No. 6. pp. 765-773.
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AU - Uchiumi, Takeshi

AU - Kinukawa, Naoko

AU - Shimada, Mitsuo

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