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

J Hepatol. 2001 Dec;35(6):765-73. doi: 10.1016/s0168-8278(01)00216-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Down-Regulation
  • Female
  • Hepatitis C / complications
  • Hepatitis C / metabolism*
  • Humans
  • Interleukin-1 / pharmacology
  • Interleukin-6 / pharmacology
  • Liver / metabolism*
  • Liver Neoplasms / complications
  • Male
  • Membrane Transport Proteins*
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Promoter Regions, Genetic / drug effects
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / metabolism
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Interleukin-1
  • Interleukin-6
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • multidrug resistance-associated protein 3
  • multidrug resistance-associated protein 2
  • multidrug resistance-associated protein 1