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 - 2001

All Science Journal Classification (ASJC) codes

  • Hepatology

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    Hinoshita, E., Taguchi, K. I., 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, 35(6), 765-773. https://doi.org/10.1016/S0168-8278(01)00216-1