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http://purl.uniprot.org/citations/22470565http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22470565http://www.w3.org/2000/01/rdf-schema#comment"

Background & aims

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis and inflammation, which can further progress into fibrosis and cirrhosis. Recently, we demonstrated that combined deletion of the two main scavenger receptors, CD36 and macrophage scavenger receptor 1 (MSR1), which are important for modified cholesterol-rich lipoprotein uptake, reduced NASH. The individual contributions of these receptors to NASH and the intracellular mechanisms by which they contribute to inflammation have not been established. We hypothesize that CD36 and MSR1 contribute independently to the onset of inflammation in NASH, by affecting intracellular cholesterol distribution inside Kupffer cells (KCs).

Methods & results

Ldlr(-/-) mice were transplanted with wild-type (Wt), Cd36(-/-) or Msr1(-/-) bone marrow and fed a Western diet for 3 months. Cd36(-/-)- and Msr1(-/-)-transplanted (tp) mice showed a similar reduction in hepatic inflammation compared to Wt-tp mice. While the total amount of cholesterol inside KCs was similar in all groups, KCs of Cd36(-/-)- and Msr1(-/-)-tp mice showed increased cytoplasmic cholesterol accumulation, while Wt-tp mice showed increased lysosomal cholesterol accumulation.

Conclusion

CD36 and MSR1 contribute similarly and independently to the progression of inflammation in NASH. One possible explanation for the inflammatory response related to expression of these receptors could be abnormal cholesterol trafficking in KCs. These data provide a new basis for prevention and treatment of NASH."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0034378"xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/author"Hofker M.H."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/author"Lutjohann D."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/author"Febbraio M."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/author"Gijbels M.J."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/author"Binder C.J."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/author"van Gorp P.J."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/author"Shiri-Sverdlov R."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/author"Verheyen F."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/author"Wouters K."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/author"Bieghs V."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/author"Hendrikx T."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/pages"e34378"xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/title"Internalization of modified lipids by CD36 and SR-A leads to hepatic inflammation and lysosomal cholesterol storage in Kupffer cells."xsd:string
http://purl.uniprot.org/citations/22470565http://purl.uniprot.org/core/volume"7"xsd:string
http://purl.uniprot.org/citations/22470565http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22470565
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http://purl.uniprot.org/uniprot/#_A0A1L1SRE8-mappedCitation-22470565http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22470565
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http://purl.uniprot.org/uniprot/#_E7D893-mappedCitation-22470565http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22470565
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