Down-regulation of intestinal scavenger receptor class B, type I (SR-BI) expression in rodents under conditions of deficient bile delivery to the intestine

Biochem J. 2001 Jun 1;356(Pt 2):317-25. doi: 10.1042/0264-6021:3560317.


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 7alpha-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 approximately 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 approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP-Binding Cassette Transporters / genetics
  • Animals
  • Base Sequence
  • Bile / metabolism*
  • Bile Ducts
  • CD36 Antigens / genetics*
  • CD36 Antigens / metabolism*
  • Cholesterol / metabolism
  • Cholesterol 7-alpha-Hydroxylase / deficiency
  • Cholesterol 7-alpha-Hydroxylase / genetics
  • DNA Primers / genetics
  • Down-Regulation
  • Enterohepatic Circulation
  • Intestinal Absorption
  • Intestinal Mucosa / metabolism*
  • Ligation
  • Male
  • Membrane Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Immunologic*
  • Receptors, Lipoprotein*
  • Receptors, Scavenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Scavenger Receptors, Class B


  • ATP Binding Cassette Transporter, Subfamily B
  • ATP-Binding Cassette Transporters
  • CD36 Antigens
  • DNA Primers
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Immunologic
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • Scarb1 protein, mouse
  • Scarb1 protein, rat
  • Scavenger Receptors, Class B
  • Cholesterol
  • multidrug resistance protein 3
  • Cholesterol 7-alpha-Hydroxylase