Scavenger receptor class B, type I (SR-BI) is expressed in the intestines of rodents and has been suggested to be involved in the absorption of dietary cholesterol. The aim of this study was to determine whether intestinal SR-BI expression is affected in animal models with altered bile delivery to the intestine and impaired cholesterol absorption. SR-BI protein and mRNA levels were determined in proximal and distal small intestine from control, bile-duct-ligated and bile-diverted rats and from control and bile-duct-ligated mice. Two genetically altered mouse models were studied: multidrug resistance-2 P-glycoprotein-deficient [Mdr2(−/−)] mice that produce phospholipid/cholesterol-free bile, and cholesterol 7α-hydroxylase-deficient [Cyp7a(−/−)] mice, which exhibit qualitative and quantitative changes in the bile-salt pool. Cholesterol-absorption efficiency was quantified using a dual-isotope ratio method. SR-BI was present at the apical membrane of enterocytes in control rats and mice and was more abundant in proximal than in distal segments of the intestine. In bile-duct-ligated animals, levels of SR-BI protein were virtually absent and mRNA levels were decreased by ≈ 50%. Bile-diverted rats, Mdr2(−/−) mice and Cyp7a(−/−) mice showed decreased levels of intestinal SR-BI protein while mRNA levels were unaffected. Cholesterol absorption was reduced by > 90% in bile-duct-ligated and bile-diverted animals and in Cyp7a(−/−) mice, whereas Mdr2(−/−) mice showed an ≈ 50% reduction. This study shows that SR-BI is expressed at the apical membrane of enterocytes of rats and mice, mainly in the upper intestine where cholesterol absorption is greatest, and indicates that bile components play a role in post-transcriptional regulation of SR-BI expression. Factors associated with cholestasis appear to be involved in transcriptional control of intestinal SR-BI expression. The role of SR-BI in the cholesterol-absorption process remains to be defined.
Abbreviations used: HMGR, 3-hydroxy-3-methylglutaryl CoA reductase; mdr2/Mdr2, multidrug resistance-2 protein/gene; Cyp7a, cholesterol 7α-hydroxylase gene; SR-BI, scavenger receptor class B, type I; BBM, brush-border membrane; RT-PCR, reverse transcriptase PCR.