SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Buczacki SJA)
 

Sökning: WFRF:(Buczacki SJA) > (2023) > FXR inhibition may ...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005030naa a2201189 4500
001oai:prod.swepub.kib.ki.se:152015779
003SwePub
008240701s2023 | |||||||||||000 ||eng|
024a http://kipublications.ki.se/Default.aspx?queryparsed=id:1520157792 URI
024a https://doi.org/10.1038/s41586-022-05594-02 DOI
040 a (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Brevini, T4 aut
2451 0a FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
264 c 2022-12-05
264 1b Springer Science and Business Media LLC,c 2023
520 a Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.
700a Maes, M4 aut
700a Webb, GJ4 aut
700a John, BV4 aut
700a Fuchs, CD4 aut
700a Buescher, G4 aut
700a Wang, L4 aut
700a Griffiths, C4 aut
700a Brown, ML4 aut
700a Scott, WE4 aut
700a Pereyra-Gerber, P4 aut
700a Gelson, WTH4 aut
700a Brown, S4 aut
700a Dillon, S4 aut
700a Muraro, D4 aut
700a Sharp, J4 aut
700a Neary, M4 aut
700a Box, H4 aut
700a Tatham, L4 aut
700a Stewart, J4 aut
700a Curley, P4 aut
700a Pertinez, H4 aut
700a Forrest, S4 aut
700a Mlcochova, P4 aut
700a Varankar, SS4 aut
700a Darvish-Damavandi, M4 aut
700a Mulcahy, VL4 aut
700a Kuc, RE4 aut
700a Williams, TL4 aut
700a Heslop, JA4 aut
700a Rossetti, D4 aut
700a Tysoe, OC4 aut
700a Galanakis, V4 aut
700a Vila-Gonzalez, M4 aut
700a Crozier, TWM4 aut
700a Bargehr, J4 aut
700a Sinha, S4 aut
700a Upponi, SS4 aut
700a Fear, C4 aut
700a Swift, L4 aut
700a Saeb-Parsy, K4 aut
700a Davies, SE4 aut
700a Wester, Au Karolinska Institutet4 aut
700a Hagstrom, Hu Karolinska Institutet4 aut
700a Melum, E4 aut
700a Clements, D4 aut
700a Humphreys, P4 aut
700a Herriott, J4 aut
700a Kijak, E4 aut
700a Cox, H4 aut
700a Bramwell, C4 aut
700a Valentijn, A4 aut
700a Illingworth, CJR4 aut
700a Dahman, B4 aut
700a Bastaich, DR4 aut
700a Ferreira, RD4 aut
700a Marjot, T4 aut
700a Barnes, E4 aut
700a Moon, AM4 aut
700a Barritt, AS4 aut
700a Gupta, RK4 aut
700a Baker, S4 aut
700a Davenport, AP4 aut
700a Corbett, G4 aut
700a Gorgoulis, VG4 aut
700a Buczacki, SJA4 aut
700a Lee, JH4 aut
700a Matheson, NJ4 aut
700a Trauner, M4 aut
700a Fisher, AJ4 aut
700a Gibbs, P4 aut
700a Butler, AJ4 aut
700a Watson, CJE4 aut
700a Mells, GF4 aut
700a Dougan, G4 aut
700a Owen, A4 aut
700a Lohse, AW4 aut
700a Vallier, L4 aut
700a Sampaziotis, F4 aut
710a Karolinska Institutet4 org
773t Natured : Springer Science and Business Media LLCg 615:7950, s. 134-+q 615:7950<134-+x 1476-4687x 0028-0836
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:152015779
8564 8u https://doi.org/10.1038/s41586-022-05594-0

Hitta via bibliotek

  • Nature (Sök värdpublikationen i LIBRIS)

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy