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Abnormal hepatic expression of fibrillin-1 in children with cholestasis
Thierry Lamireau1, Liliane Dubuisson, Sébastien Lepreux
1Groupe de Recherches pour l'Etude du Foie, Université Victor Segalen, Bordeaux, France.
Insights
Fibrillin-1 is overexpressed in fibrotic liver diseases in children. Enhanced deposition occurs in severe cholestatic conditions, but its association with bile ducts is altered, except in biliary atresia.
Area of Science:
- Hepatology
- Pediatric Gastroenterology
- Extracellular Matrix Biology
Background:
- Fibrillin-1 is a key component of microfibrils and is found in normal adult liver.
- Fibrillin-1 is overexpressed in fibrotic areas associated with liver cirrhosis and hepatocellular carcinoma.
Purpose of the Study:
- To investigate fibrillin-1 expression in pediatric cholestatic liver diseases.
- To compare fibrillin-1 distribution in normal pediatric liver with various cholestatic conditions.
Main Methods:
- Immunohistochemistry was used to analyze fibrillin-1 expression in liver biopsies.
- Samples included children with paucity of intrahepatic bile ducts, biliary atresia, and other cholestatic diseases.
- Histologically normal liver samples served as controls.
Main Results:
- In normal pediatric liver, fibrillin-1 was detected in vessel walls, sinusoids, and portal connective tissue.
- Enhanced fibrillin-1 deposition was observed in fibrotic portal areas and septa in severe cholestatic diseases.
- Loss of fibrillin-1 expression near bile duct basement membranes occurred in most cholestatic diseases, except biliary atresia.
- Fibrillin-1 co-localized with alphaVbeta3 integrin in sinusoids but not around biliary structures.
Conclusions:
- Fibrillin-1 deposition is significantly increased in pediatric cholestatic liver diseases with severe fibrosis.
- Altered fibrillin-1 expression around biliary structures may indicate disease-specific changes.
- Fibrillin-1 and alphaVbeta3 integrin interactions in sinusoids are preserved in these conditions.
Abstract:
Fibrillin-1, one of the main constituents of microfibrils, is present in normal adult liver and overexpressed in fibrotic area around cirrhotic nodules and hepatocellular carcinoma. In this work fibrillin-1 expression was studied by immunohistochemistry in liver samples from children with various cholestatic diseases corresponding to paucity of intrahepatic bile ducts, biliary atresia, congenital hepatic fibrosis, Byler's disease, mitochondrial cytopathy, sclerosing cholangitis, or choledochal cyst. As controls, histologically normal liver samples were used. In control liver, as in adult, fibrillin-1 was expressed in vessel walls, sinusoids, and portal connective tissue, particularly at the interface with the limiting hepatocytic plate and close to the basement membrane of bile ducts. In paucity of intrahepatic bile ducts without fibrosis, the fibrillin-1 distribution was similar to controls. In cholestatic diseases associated with severe fibrosis, such as biliary atresia, congenital hepatic fibrosis, Byler's disease, mitochondrial cytopathy, or sclerosing cholangitis, an enhanced deposition of fibrillin-1 was observed in portal connective tissue and fibrous septa. The strong fibrillin-1 expression close to the basement membrane of biliary structures was lost in cholestatic diseases, except biliary atresia. Finally, in normal and pathologic tissues, fibrillin-1 was co-localized with its putative receptor alphaVbeta3 in sinusoids but not around biliary structures.