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Regenerative stimulus increases hepatocyte tight junctional permeability.
S Poucell1, W G Hardison, K Miyai
1Department of Pathology, University of California, San Diego School of Medicine 92093.
Hepatology (Baltimore, Md.)
|October 1, 1992
Summary
Liver regeneration after two-thirds hepatectomy increases biliary permeability. Tight junction alterations allow greater molecular and charge-selective passage into bile, facilitating liver repair.
Area of Science:
- Hepatology
- Cell Biology
- Gastroenterology
Background:
- Liver regeneration involves significant architectural remodeling.
- Tight junctions regulate permeability in various tissues, including the liver.
- Previous studies suggest altered tight junctional permeability during liver remodeling.
Purpose of the Study:
- To correlate changes in tight junction morphometry with biliary permeability after two-thirds hepatectomy.
- To assess the impact of hepatectomy on the biliary tree's permeability to different molecules.
- To understand the role of tight junctions in liver regeneration.
Main Methods:
- Two-thirds hepatectomy in animal models.
- Freeze-fracture electron microscopy to examine tight junction morphology.
- Assessment of biliary permeability using sucrose and horseradish peroxidase.
- Analysis of biliary outputs of anionic and cationic cholephilic probes.
Main Results:
- Reduced tight junctional strand counts, density, and altered orientation 24 hours post-hepatectomy.
- Increased paracellular access of sucrose and horseradish peroxidase into bile.
- Decreased biliary output of low molecular weight and cationic probes.
- Evidence of increased, yet charge-selective, biliary permeability.
Conclusions:
- Two-thirds hepatectomy induces significant alterations in biliary tight junctions.
- These morphological changes lead to increased, charge-selective biliary permeability.
- Loosening or lysis of intercellular junctions is likely necessary for hepatocellular regenerative reorganization.