Sökning: WFRF:(Dillon John) > FXR inhibition may ...
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000 | 05030naa a2201189 4500 | |
001 | oai:prod.swepub.kib.ki.se:152015779 | |
003 | SwePub | |
008 | 240811s2023 | |||||||||||000 ||eng| | |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1520157792 URI |
024 | 7 | a https://doi.org/10.1038/s41586-022-05594-02 DOI |
040 | a (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Brevini, T4 aut |
245 | 1 0 | a FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2 |
264 | c 2022-12-05 | |
264 | 1 | b 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. | |
700 | 1 | a Maes, M4 aut |
700 | 1 | a Webb, GJ4 aut |
700 | 1 | a John, BV4 aut |
700 | 1 | a Fuchs, CD4 aut |
700 | 1 | a Buescher, G4 aut |
700 | 1 | a Wang, L4 aut |
700 | 1 | a Griffiths, C4 aut |
700 | 1 | a Brown, ML4 aut |
700 | 1 | a Scott, WE4 aut |
700 | 1 | a Pereyra-Gerber, P4 aut |
700 | 1 | a Gelson, WTH4 aut |
700 | 1 | a Brown, S4 aut |
700 | 1 | a Dillon, S4 aut |
700 | 1 | a Muraro, D4 aut |
700 | 1 | a Sharp, J4 aut |
700 | 1 | a Neary, M4 aut |
700 | 1 | a Box, H4 aut |
700 | 1 | a Tatham, L4 aut |
700 | 1 | a Stewart, J4 aut |
700 | 1 | a Curley, P4 aut |
700 | 1 | a Pertinez, H4 aut |
700 | 1 | a Forrest, S4 aut |
700 | 1 | a Mlcochova, P4 aut |
700 | 1 | a Varankar, SS4 aut |
700 | 1 | a Darvish-Damavandi, M4 aut |
700 | 1 | a Mulcahy, VL4 aut |
700 | 1 | a Kuc, RE4 aut |
700 | 1 | a Williams, TL4 aut |
700 | 1 | a Heslop, JA4 aut |
700 | 1 | a Rossetti, D4 aut |
700 | 1 | a Tysoe, OC4 aut |
700 | 1 | a Galanakis, V4 aut |
700 | 1 | a Vila-Gonzalez, M4 aut |
700 | 1 | a Crozier, TWM4 aut |
700 | 1 | a Bargehr, J4 aut |
700 | 1 | a Sinha, S4 aut |
700 | 1 | a Upponi, SS4 aut |
700 | 1 | a Fear, C4 aut |
700 | 1 | a Swift, L4 aut |
700 | 1 | a Saeb-Parsy, K4 aut |
700 | 1 | a Davies, SE4 aut |
700 | 1 | a Wester, Au Karolinska Institutet4 aut |
700 | 1 | a Hagstrom, Hu Karolinska Institutet4 aut |
700 | 1 | a Melum, E4 aut |
700 | 1 | a Clements, D4 aut |
700 | 1 | a Humphreys, P4 aut |
700 | 1 | a Herriott, J4 aut |
700 | 1 | a Kijak, E4 aut |
700 | 1 | a Cox, H4 aut |
700 | 1 | a Bramwell, C4 aut |
700 | 1 | a Valentijn, A4 aut |
700 | 1 | a Illingworth, CJR4 aut |
700 | 1 | a Dahman, B4 aut |
700 | 1 | a Bastaich, DR4 aut |
700 | 1 | a Ferreira, RD4 aut |
700 | 1 | a Marjot, T4 aut |
700 | 1 | a Barnes, E4 aut |
700 | 1 | a Moon, AM4 aut |
700 | 1 | a Barritt, AS4 aut |
700 | 1 | a Gupta, RK4 aut |
700 | 1 | a Baker, S4 aut |
700 | 1 | a Davenport, AP4 aut |
700 | 1 | a Corbett, G4 aut |
700 | 1 | a Gorgoulis, VG4 aut |
700 | 1 | a Buczacki, SJA4 aut |
700 | 1 | a Lee, JH4 aut |
700 | 1 | a Matheson, NJ4 aut |
700 | 1 | a Trauner, M4 aut |
700 | 1 | a Fisher, AJ4 aut |
700 | 1 | a Gibbs, P4 aut |
700 | 1 | a Butler, AJ4 aut |
700 | 1 | a Watson, CJE4 aut |
700 | 1 | a Mells, GF4 aut |
700 | 1 | a Dougan, G4 aut |
700 | 1 | a Owen, A4 aut |
700 | 1 | a Lohse, AW4 aut |
700 | 1 | a Vallier, L4 aut |
700 | 1 | a Sampaziotis, F4 aut |
710 | 2 | a Karolinska Institutet4 org |
773 | 0 | t Natured : Springer Science and Business Media LLCg 615:7950, s. 134-+q 615:7950<134-+x 1476-4687x 0028-0836 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:152015779 |
856 | 4 8 | u https://doi.org/10.1038/s41586-022-05594-0 |
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