Fig. 1: FXR modulates ACE2 expression and SARS-CoV-2 infection.
From: FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
a, ChIP–qPCR on cholangiocyte organoids, showing that the FXR agonist CDCA promotes the binding of FXR on the ACE2 promoter, and that this is reduced by FXR inhibitors (UDCA and ZGG). OSTα as positive control; ACE2 promoter adjoining region as negative control; n = 4 independent experiments; one-way ANOVA adjusted for multiple comparisons; bars,s.d. b, Schematic representation of the suggested mechanism for FXR-mediated control of ACE2 expression and SARS-CoV-2 infection relative to e,f. c,d, qPCR (c) and immunofluorescence (d) showing the levels of ACE2 after modulation of FXR activity in primary airway, biliary and intestinal organoids. Housekeeping gene, HMBS (also known as PBGD); n = 4 independent experiments; one-way ANOVA; centre line, median; box, interquartile range (IQR); whiskers, range; bars, s.d. Yellow scale bars, 50 μm; grey scale bars, 25 μm. e, qPCR quantifying SARS-CoV-2 viral RNA 24 h after infection in primary organoids treated with physiological levels of bile acids (CDCA) in the presence or absence of FXR inhibitors (UDCA and ZGG). Housekeeping gene, GAPDH; n = 4 independent experiments; one-way ANOVA adjusted for multiple comparisons; centre line, median; box, interquartile range (IQR); whiskers, range; bars, s.d. f, Immunofluorescence images showing the presence of SARS-CoV-2 spike protein 24 hours after infection in organoids corresponding to e. Scale bars, 25 μm. CDCA, UDCA and ZGG concentration, 10 μM.
