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Background and aims

The secretion of bile salts transported by the bile salt export pump (BSEP) is the primary driving force for the generation of bile flow; thus, it is closely related to the formation of cholesterol stones. Caveolin-1 (Cav-1), an essential player in cell signalling and endocytosis, is known to co-localize with cholesterol-rich membrane domains. This study illustrates the role of Cav-1 and BSEP in cholesterol stone formation.

Methods

Adult male C57BL/6 mice were used as an animal model. HepG2 cells were cultured under different cholesterol concentrations and BSEP, Cav-1, p-PKCα and Hax-1 expression levels were determined via Western blotting. Expression levels of BSEP and Cav-1 mRNA were detected using real-time PCR. Immunofluorescence and immunoprecipitation assays were performed to study BSEP and Hax-1 distribution. Finally, an ATPase activity assay was performed to detect BSEP transport activity under different cholesterol concentrations in cells.

Results

Under low-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels significantly increased, PKCα phosphorylation significantly decreased, BSEP binding capacity to Hax-1 weakened, and BSEP function increased. Under high-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels decreased, PKCα phosphorylation increased, BSEP binding capacity to Hax-1 rose, and BSEP function decreased.

Conclusion

Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes via PKCα-associated signalling under cholesterol stimulation."xsd:string
http://purl.uniprot.org/citations/38164042http://purl.org/dc/terms/identifier"doi:10.1111/jcmm.18110"xsd:string
http://purl.uniprot.org/citations/38164042http://purl.uniprot.org/core/author"Wu S."xsd:string
http://purl.uniprot.org/citations/38164042http://purl.uniprot.org/core/author"Cui M."xsd:string
http://purl.uniprot.org/citations/38164042http://purl.uniprot.org/core/author"Kong J."xsd:string
http://purl.uniprot.org/citations/38164042http://purl.uniprot.org/core/author"Pang L."xsd:string
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http://purl.uniprot.org/citations/38164042http://purl.uniprot.org/core/name"J Cell Mol Med"xsd:string
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http://purl.uniprot.org/citations/38164042http://purl.uniprot.org/core/title"Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes by PKCalpha-associated signalling under cholesterol stimulation."xsd:string
http://purl.uniprot.org/citations/38164042http://purl.uniprot.org/core/volume"28"xsd:string
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