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 language | English |
|---|---|
| Pages (from-to) | 765-773 |
| Number of pages | 9 |
| Journal | Journal of Hepatology |
| Volume | 35 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Dec 1 2001 |
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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 journal › Article
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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
PY - 2001/12/1
Y1 - 2001/12/1
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
VL - 35
SP - 765
EP - 773
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 6
ER -