Expresssion and Regulation of Scavenger Receptor Class B Type I (SR-BI) in Human and Murine Gallbladder Epithelial Cells

Juan Francisco Miquel:

Presentado a Congreso anual de la American Gastroenterological Association. 20 al 26 de Mayo, 2000.  San Diego, California, Estados Unidos.

Gallbladder (GB) appears to absorb a significant amount of biliary cholesterol (Chol) and lecithin secreted by the liver. This process seems to be relevant in Chol homeostasis and in reducing the Chol saturation in GB bile. The molecular mechanisms involved in lipid absorption by epithelial cells remain unknown. However, it has been recently proposed that the scavenger receptor SR-BI might play a role in intestinal Chol absorption.

Aims: To study the expression of SR-BI in human and murine GB and its regulation under conditions of increased GB bile Chol content.

Methods and Results: Human GBs with and without cholesterolosis were obtained from Chol gallstone patients subjected to cholecystectomy, and immunohistochemistry for SR-BI was performed. A strong and specific signal for SR-BI was observed in the apical domain of GB epithelial cells and in the plasma membrane of foam cells from cholesterolotic GBs. Western blot analysis for SR-BI in total membranes from human GB epithelial cells isolated by collagenase treatment showed a specific signal for the 82 kDa SR-BI protein. In C57BL/6 mice, a strong immunohistochemical signal for SR-BI was also found in GB epithelial cells. The level of SR-BI expression was similar to that observed in the mouse liver. To evaluate the effect of bile Chol content on GB SR-BI expression, mice were fed with either a 2% Chol or lithogenic diet which induce a 2.5- and 6-fold increase in GB bile Chol concentration. By western blot analysis, an inverse correlation was observed between bile Chol content and SR-BI expression in the GB: SR-BI expression was reduced by 30% in 2% Chol-fed mice and by 70% in lithogenic-diet fed animals compared to chow-fed mice.

Conclusions: 1. SR-BI is highly expressed in GB epithelial cells and in foam cells of cholesterolotic GB. 2. SR-BI is down-regulated concomitantly with diet-induced biliary Chol hypersecretion in vivo. Similarly to its suggested role in intestinal Chol transport, SR-BI might be involved in GB Chol absorption. Although SR-BI down-regulation in GB associated with increased biliary Chol content might protect the GB wall against Chol overload, it could further maintain biliary Chol saturation and thus play a role in gallstone formation (Supported by Fondecyt 8990006).