TY - JOUR
T1 - Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection
AU - Hinoshita, Eiji
AU - Taguchi, Ken ichi
AU - Inokuchi, Akihiko
AU - Uchiumi, Takeshi
AU - Kinukawa, Naoko
AU - Shimada, Mitsuo
AU - Tsuneyoshi, Masazumi
AU - Sugimachi, Keizo
AU - Kuwano, Michihiko
N1 - Funding Information:
We thank Morimasa Wada, Takanori Nakamura, Sei Haga, Takayuki Hamatsu and Masahiro Okamoto for helpful discussion. Supported by a Grant-in-Aid for Scientific Research on the Priority Area of ABC Proteins, by CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation (JST), and by the Second-Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health and Welfare of Japan.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1016/S0168-8278(01)00216-1
DO - 10.1016/S0168-8278(01)00216-1
M3 - Article
C2 - 11738104
AN - SCOPUS:0035742868
VL - 35
SP - 765
EP - 773
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 6
ER -
