Sökning: id:"swepub:oai:lup.lub.lu.se:9b87d22f-9e1c-4cf8-8fe2-9fea2c950248" >
Inhibition of HSD17...
Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis
-
- Luukkonen, Panu K. (författare)
- Minerva Foundation Institute for Medical Research,Helsinki University Central Hospital,Yale University
-
- Sakuma, Ikki (författare)
- Yale University
-
- Gaspar, Rafael C. (författare)
- Yale University
-
visa fler...
-
- Mooring, Meghan (författare)
- Yale University
-
- Nasiri, Ali (författare)
- Yale University
-
- Kahn, Mario (författare)
- Yale University
-
- Zhang, Xian Man (författare)
- Yale University
-
- Zhang, Dongyan (författare)
- Yale University
-
- Sammalkorpi, Henna (författare)
- Helsinki University Central Hospital
-
- Penttilä, Anne K. (författare)
- Helsinki University Central Hospital
-
- Orho-Melander, Marju (författare)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Skåne University Hospital
-
- Arola, Johanna (författare)
- University of Helsinki
-
- Juuti, Anne (författare)
- Helsinki University Central Hospital
-
- Zhang, Xuchen (författare)
- Yale University
-
- Yimlamai, Dean (författare)
- Yale University
-
- Yki-Järvinen, Hannele (författare)
- Minerva Foundation Institute for Medical Research,University of Helsinki
-
- Petersen, Kitt Falk (författare)
- Yale University
-
- Shulman, Gerald I. (författare)
- Yale University
-
visa färre...
-
(creator_code:org_t)
- 2023-01-20
- 2023
- Engelska.
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 120:4
- Relaterad länk:
-
http://dx.doi.org/10... (free)
-
visa fler...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, in which prognosis is determined by liver fibrosis. A common variant in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13, rs72613567-A) is associated with a reduced risk of fibrosis in NAFLD, but the underlying mechanism(s) remains unclear. We investigated the effects of this variant in the human liver and in Hsd17b13 knockdown in mice by using a state-of-the-art metabolomics approach. We demonstrate that protection against liver fibrosis conferred by the HSD17B13 rs72613567-A variant in humans and by the Hsd17b13 knockdown in mice is associated with decreased pyrimidine catabolism at the level of dihydropyrimidine dehydrogenase. Furthermore, we show that hepatic pyrimidines are depleted in two distinct mouse models of NAFLD and that inhibition of pyrimidine catabolism by gimeracil phenocopies the HSD17B13-induced protection against liver fibrosis. Our data suggest pyrimidine catabolism as a therapeutic target against the development of liver fibrosis in NAFLD.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Nyckelord
- hydroxysteroid 17-beta dehydrogenase 13
- liver fibrosis
- nonalcoholic fatty liver disease
- nonalcoholic steatohepatitis
- pyrimidines
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Luukkonen, Panu ...
-
Sakuma, Ikki
-
Gaspar, Rafael C ...
-
Mooring, Meghan
-
Nasiri, Ali
-
Kahn, Mario
-
visa fler...
-
Zhang, Xian Man
-
Zhang, Dongyan
-
Sammalkorpi, Hen ...
-
Penttilä, Anne K ...
-
Orho-Melander, M ...
-
Arola, Johanna
-
Juuti, Anne
-
Zhang, Xuchen
-
Yimlamai, Dean
-
Yki-Järvinen, Ha ...
-
Petersen, Kitt F ...
-
Shulman, Gerald ...
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Gastroenterologi
- Artiklar i publikationen
-
Proceedings of t ...
-
Proceedings of t ...
- Av lärosätet
-
Lunds universitet