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Interaction between hepatic membrane type 1 matrix metalloproteinase and acireductone dioxygenase 1 regulates

M-L Chang1,2, Y-H Huang1, J-C Cheng3

  • 1Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Journal of Viral Hepatitis
|November 6, 2015
PubMed

Insights

A physical interaction between membrane type 1 matrix metalloproteinase (MT1-MMP) and acireductone dioxygenase 1 (ADI1) suppresses hepatitis C virus (HCV) infection. This inhibitory effect can be reversed by ADI1 overexpression, offering potential therapeutic insights.

Area of Science:

  • Hepatology and Virology
  • Molecular Cell Biology
  • Biochemistry

Background:

  • Membrane type 1 matrix metalloproteinase (MT1-MMP) regulates tetraspanin-enriched microdomains and interacts with proteins involved in hepatitis C virus (HCV) entry, such as claudin-1 and acireductone dioxygenase 1 (ADI1).
  • Understanding the interplay between MT1-MMP, ADI1, and HCV is crucial for developing novel therapeutic strategies against chronic HCV infection.

Purpose of the Study:

  • To investigate the hepatic expression of MT1-MMP, ADI1, and claudin-1 in chronic hepatitis C patients.
  • To examine the physical interaction between MT1-MMP and ADI1 in relation to HCV RNA levels.
  • To elucidate the role of MT1-MMP and ADI1 interaction in modulating HCV cell entry and infection.

Main Methods:

  • Analysis of 104 liver biopsies from chronic hepatitis C patients and 84 liver tissues from HCV-related hepatocellular carcinoma.
  • Assessment of MT1-MMP and ADI1 interaction using co-immunoprecipitation assays.
  • Evaluation of HCV pseudoparticles and HCVcc infection in Huh7.5 cells with MT1-MMP and ADI1 overexpression.

Main Results:

  • Positive cytoplasmic ADI1 expression correlated with higher serum HCV RNA levels.
  • MT1-MMP and ADI1 interaction was associated with lower intrahepatic HCV RNA levels.
  • Overexpression of MT1-MMP suppressed HCV entry, an effect reversed by ADI1 co-expression.

Conclusions:

  • The physical interaction between MT1-MMP and ADI1 plays a significant role in suppressing HCV infection.
  • MT1-MMP-ADI1 interaction presents a potential therapeutic target for inhibiting HCV replication.
  • ADI1 overexpression can reverse the inhibitory effect of MT1-MMP on HCV, suggesting a dose-dependent mechanism.
Keywords:
acireductone dioxygenase 1hepatitis C virusmembrane type-1 matrix metalloproteinase

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