title: Differential basolateral-apical distribution of scavenger receptor, class B, type I in cultured cells and the liver.
abstract: The high-density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), mediates selective cholesteryl ester uptake into the liver, which finally results in cholesterol secretion into the bile. Despite several reports, the distribution of hepatic SR-BI between the sinusoidal and canalicular membranes is still under debate. We present immunohistological data using specific markers showing that the bulk of SR-BI is present in sinusoidal membranes and, to a lesser extent, in canalicular membranes in murine and human liver sections. In addition, SR-BI was detected in preparations of rat liver canalicular membranes. We also compared the in vivo findings to HepG2 cells, a widely used in vitro hepatocyte model. Interestingly, SR-BI was enriched in bile canalicular-like (BC-like) structures in polarized HepG2 cells, which were cultivated either conventionally to form a monolayer or in Matrigel to form three-dimensional structures. Fluorescently labeled HDL was transported into close proximity of BC-like structures, whereas HDL labeled with the fluorescent cholesterol analog BODIPY-cholesterol was clearly detected within these structures. Importantly, similarly to human and mouse liver, SR-BI was localized in basolateral membranes in three-dimensional liver microtissues from primary human liver cells. Our results demonstrate that SR-BI is highly enriched in sinusoidal membranes and is also found in canalicular membranes. There was no significant basolateral-apical redistribution of hepatic SR-BI in fasting and refeeding experiments in mice. Furthermore, in vitro studies in polarized HepG2 cells showed explicit differences as SR-BI was highly enriched in BC-like structures. These structures are, however, functional and accumulated HDL-derived cholesterol. Thus, biological relevant model systems should be employed when investigating SR-BI distribution in vitro.
authors: Center for Pathobiochemistry and Genetics, Department of Medical Chemistry, Medical University of Vienna, Währingerstraße 10, 1090, Vienna, Austria.
authors: Stefanie
authors: S
authors: Fruhwürth
authors: Werner J
authors: WJ
authors: Kovacs
authors: Robert
authors: R
authors: Bittman
authors: Simon
authors: S
authors: Messner
authors: Clemens
authors: C
authors: Röhrl
authors: Herbert
authors: H
authors: Stangl
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051122:Scavenger Receptors, Class B / Q000378:metabolism*
chemical_list: D051122:Scavenger Receptors, Class B