(A) The expression of c-fos in isolated
IECs, as determined by RNA-sequencing analysis as Figure 1.
(B) Fut2 promoter activity as demonstrated with luciferase
activity. Naïve-AP1 represents fut2 promoter with
naïve AP-1 binding site and Mut-AP1 represents fut2
promoter with mutated AP-1 binding site as indicated in the figure. The number
indicates the position AP-1 site with the start of first exon set as +1. Data
were shown as relative luciferase activity with the ratio of Dox:vehicle. Mean
± SEM, ***p < 0.001, ns not significant.
(C) Representative western blot image of p-Erk1/2 in ileal
IECs stimulated with VIP (100 nM) for the indicated time.
(D) C-fos mRNA and Fut2 expression in intestinal organoid
cultures from WT mice or from
VIPR1−/−
stimulated with/without VIP in the presence or absence of Erk1/2 inhibitor
(FR180204, 50 μM) for 12 h. (B-D) Data are representative of three
independent experiments.
(E) Immunofluorescence section and quantification for C-fos
(red) or p-Erk1/2 (red) with EpCAM (green) and DAPI staining of ileum in WT mice
12h after injection with PBS or VIP (6 μg/mice).
(F-G) Immunofluorescence section and quantification for
C-fos (red) or p-Erk1/2 (red) with EpCAM (green) and DAPI staining of ileum in
VipIRES-crehM3Dqfl/+
mice (F, activating DREADD) or
VipIRES-crehM4Difl/fl
mice (G, inhibitory DREADD) after treatment with vehicle or CNO. (E-G) Data are
representative of at least 5 mice per condition. Scale bar, 50 μm. * p
< 0.05, **p < 0.01.