Search: onr:"swepub:oai:prod.swepub.kib.ki.se:135004302" >
Disrupting Hepatocy...
Disrupting Hepatocyte Cyp51 from Cholesterol Synthesis Leads to Progressive Liver Injury in the Developing Mouse and Decreases RORC Signalling
-
Urlep, Z (author)
-
Lorbek, G (author)
-
Perse, M (author)
-
show more...
-
Jeruc, J (author)
-
Juvan, P (author)
-
Matz-Soja, M (author)
-
Gebhardt, R (author)
-
- Bjorkhem, I (author)
- Karolinska Institutet
-
Hall, JA (author)
-
Bonneau, R (author)
-
Littman, DR (author)
-
Rozman, D (author)
-
show less...
-
(creator_code:org_t)
- 2017-01-18
- 2017
- English.
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7, s. 40775-
- Related links:
-
https://doi.org/10.1...
-
show more...
-
http://kipublication...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Development of mice with hepatocyte knockout of lanosterol 14α-demethylase (HCyp51−/−) from cholesterol synthesis is characterized by the progressive onset of liver injury with ductular reaction and fibrosis. These changes begin during puberty and are generally more aggravated in the knockout females. However, a subgroup of (pre)pubertal knockout mice (runts) exhibits a pronounced male prevalent liver dysfunction characterized by downregulated amino acid metabolism and elevated Casp12. RORC transcriptional activity is diminished in livers of all runt mice, in correlation with the depletion of potential RORC ligands subsequent to CYP51 disruption. Further evidence for this comes from the global analysis that identified a crucial overlap between hepatic Cyp51−/− and Rorc−/− expression profiles. Additionally, the reduction in RORA and RORC transcriptional activity was greater in adult HCyp51−/− females than males, which correlates well with their downregulated amino and fatty acid metabolism. Overall, we identify a global and sex-dependent transcriptional de-regulation due to the block in cholesterol synthesis during development of the Cyp51 knockout mice and provide in vivo evidence that sterol intermediates downstream of lanosterol may regulate the hepatic RORC activity.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Urlep, Z
-
Lorbek, G
-
Perse, M
-
Jeruc, J
-
Juvan, P
-
Matz-Soja, M
-
show more...
-
Gebhardt, R
-
Bjorkhem, I
-
Hall, JA
-
Bonneau, R
-
Littman, DR
-
Rozman, D
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Gastroenterology ...
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Cell and Molecul ...
- Articles in the publication
-
Scientific repor ...
- By the university
-
Karolinska Institutet