Elevated expression of caveolin-1 at protein and mRNA level in human cirrhotic liver: relation with nitric oxide

Abstract

Background. Caveolin, the principal structural protein of caveolae, binds with endothelial nitric oxide synthase (eNOS) leading to enzyme inhibition. This study examined the expression of caveolin and eNOS at the protein and mRNA levels in patients with hepatocellular carcinoma and hepatitis C-related cirrhosis, and in control noncirrhotic liver specimens obtained from patients with metastatic liver carcinoma. Methods. Anti-eNOS, anti-caveoin-1, and anti-calmodulin antibodies were used for Western blotting. For in situ hybridization (ISH), human eNOS and caveolin-1 peptide nucleic acid probes were used with a catalyzed signal amplification system. Results. Western blotting showed marked overexpression of caveolin-1 protein in cirrhotic liver, while caveolin-1 was almost undetectable in control liver tissue. Endothelial NOS was expressed at a slightly higher level in cirrhotic liver than in control liver tissue. Calmodulin was expressed abundantly in control liver tissue and at a low level in cirrhotic liver tissue. By ISH, eNOS mRNA was localized on portal vein and hepatic lining cells, and caveolin-1 mRNA was almost undetectable in normal liver tissue. In cirrhotic liver tissue, caveolin-1 mRNA was overexpressed on hepatic sinusoidal lining cells, while eNOS mRNA expression was similar to that in normal liver. Conclusions. Enhanced caveolin-1 expression may be associated with a significant reduction in NO catalytic activity in cirrhosis.