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Lessons from hepatocyte-specific cyp51 knockout mice : impaired cholesterol synthesis leads to oval cell-driven liver injury
Keber, Rok (Avtor), Lorbek, Gregor (Avtor), Lewinska, Monika (Avtor), Juvan, Peter (Avtor), Perše, Martina (Avtor), Bjorkhem, Ingemar (Avtor), Rozman, Damjana (Avtor), Horvat, Simon (Avtor), Jeruc, Jera (Avtor), Gutiérrez Mariscal, Francisco Miguel (Avtor), Gebhardt, Rolf (Avtor)

URLURL - Predstavitvena datoteka, za dostop obiščite http://www.nature.com/srep/2015/150305/srep08777/full/srep08777.html Novo okno

Izvleček
We demonstrate unequivocally that defective cholesterol synthesis is an independent determinant of liver inflammation and fibrosis. We prepared a mouse hepatocyte-specific knockout (LKO) of lanosterol 14 a -demethylase (CYP51) from the part of cholesterol synthesis that is already committed to cholesterol. LKO mice developed hepatomegaly with oval cell proliferation, fibrosis and inflammation, but without steatosis. The key trigger was reduced cholesterol esters that provoked cell cycle arrest, senescence-associated secretory phenotype and ultimately the oval cell response, while elevated CYP51 substrates promoted the integrated stress response. In spite of the oval cell-driven fibrosis being histologically similar in both sexes, data indicates a female-biased down-regulation of primary metabolism pathways and a stronger immune response in males. Liver injury was ameliorated by dietary fats predominantly in females, whereas dietary cholesterol rectified fibrosis in both sexes. Our data place defective cholesterol synthesis as a focus of sex-dependent liver pathologies.

Jezik:Angleški jezik
Ključne besede:cholesterol synthesis, hepatocyte, liver injury
Vrsta gradiva:Delo ni kategorizirano (r6)
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:MF - Medicinska fakulteta
Leto izida:2015
Št. strani:str. 1-11
Številčenje:Vol. 5, art. no.8777
UDK:616.4
ISSN pri članku:2045-2322
DOI:10.1038/srep08777 Povezava se odpre v novem oknu
COBISS.SI-ID:31858137 Povezava se odpre v novem oknu
Število ogledov:459
Število prenosov:228
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
 
Skupna ocena:(0 glasov)
Vaša ocena:Ocenjevanje je dovoljeno samo prijavljenim uporabnikom.
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Gradivo je del revije

Naslov:Scientific reports
Založnik:Nature Publishing Group
ISSN:2045-2322
COBISS.SI-ID:18727432 Novo okno

Sekundarni jezik

Jezik:Neznan jezik
Ključne besede:sinteza holesterola, hepatociti, okvare jeter

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