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Alterations in tight junctions differ between primary biliary cirrhosis and primary sclerosing cholangitis
S Sakisaka1, T Kawaguchi, E Taniguchi
1Third Department of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan. sakisaka@fukuoka-u.ac.jp
Hepatology (Baltimore, Md.)
|June 8, 2001
Summary
Alterations in tight junction proteins like 7H6 are prominent in bile ducts in primary biliary cirrhosis (PBC) and hepatocytes in primary sclerosing cholangitis (PSC), suggesting distinct pathways for bile regurgitation in these liver diseases.
Area of Science:
- Hepatology
- Cell Biology
- Immunohistochemistry
Background:
- Tight junctions (TJ) in biliary epithelial cells (BEC) and hepatocytes are crucial for preventing bile regurgitation.
- Dysfunction of TJs is implicated in chronic cholestatic liver diseases like primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC).
Purpose of the Study:
- To investigate the localization of two key TJ proteins, ZO-1 and 7H6, in BEC and hepatocytes in PBC and PSC.
- To determine if TJ alterations correlate with disease pathology and suggest mechanisms for bile regurgitation.
Main Methods:
- Double-fluorescence immunohistochemistry was performed on frozen liver sections from patients with PBC, PSC, extrahepatic cholestasis (Ex-C), hepatitis C-associated cirrhosis (LC-C), and normal controls.
- Localization and preservation of ZO-1 and 7H6 proteins in bile ducts and hepatocytes were assessed.
Main Results:
- In normal livers and cirrhosis, ZO-1 and 7H6 colocalized in bile ducts and between hepatocytes.
- In untreated PBC, 7H6 staining was diminished/absent in bile ducts, while ZO-1 was preserved.
- In PSC and Ex-C, both ZO-1 and 7H6 were preserved in bile ducts, but 7H6 frequently disappeared in hepatocytes.
- A significant reduction in 7H6-positive bile ducts (relative to ZO-1) was observed in PBC compared to other conditions.
Conclusions:
- Primary biliary cirrhosis (PBC) exhibits substantial alterations in tight junction protein 7H6 predominantly within bile ducts.
- Primary sclerosing cholangitis (PSC) shows significant alterations in tight junction protein 7H6 primarily in hepatocytes.
- These distinct TJ protein alterations suggest different paracellular permeability routes contributing to bile regurgitation in these chronic cholestatic liver diseases.