Fig. 2: Mineralocorticoid receptor (MR) antagonism by spironolactone decreases intestinal fibrosis in mice with chronic colitis. | Nature Communications

Fig. 2: Mineralocorticoid receptor (MR) antagonism by spironolactone decreases intestinal fibrosis in mice with chronic colitis.

From: Mineralocorticoid receptor activation contributes to intestinal fibrosis through neutrophil gelatinase-associated lipocalin in preclinical models

Fig. 2

a–f Pharmacological inhibition of MR by spironolactone in male mice with dextran sulfate sodium (DSS)-induced chronic colitis. Male C57BL/6 J mice underwent 3 cycles of 2% DSS in their drinking water for 7 days, followed by 14 days of regular water (DSS, n = 11) for both first cycles and 7 days for the third cycle whereas control mice received normal water (CT, n = 10). Mice were subjected to either a standard diet or diet supplemented with spironolactone (30 mg.kg−1; DSS+Sp, n = 12) throughout the experiment. (a) Colonic relative mRNA levels encoding for Tgfb1, Smad2, Smad3, Mmp3, Mmp9, Timp1 and Tnf (n = 9 for CT, n = 11 for DSS, n = 12 for DSS+Sp; ordinary one way ANOVA with Tukey’s multiple comparisons test). b Representative western blot and relative protein expression of colon COL1 (n = 10 for CT, n = 11 for DSS, n = 12 for DSS+Sp; ordinary one way ANOVA with Tukey’s multiple comparisons test). c Sirius red stained colon sections, fibrosis score and collagen area fraction (n = 9 for CT, n = 11 for DSS, n = 12 for DSS+Sp; Kruskal-Wallis test with Dunn’s multiple comparisons test). d Representative gelatin zymography and quantification of colon MMP-9 (n = 10 for CT, n = 11 for DSS, n = 12 for DSS+Sp; Kruskal-Wallis test with Dunn’s multiple comparisons test) and −2 (n = 10 for CT, n = 11 for DSS, n = 11 for DSS+Sp; ordinary one way ANOVA with Tukey’s multiple comparisons test) activities. e Colonic TGF-β1 level (n = 10 for CT, n = 11 for DSS, n = 12 for DSS+Sp; ordinary one way ANOVA with Tukey’s multiple comparisons test). (f) Representative western blot and relative protein expression of phospho-SMAD 2/3 (p-SMAD2, p-SMAD3) and SMAD 2/3 (n = 6 for CT, n = 8 for DSS, n = 8 for DSS+Sp; ordinary one way ANOVA with Tukey’s multiple comparisons test for p-Smad2/Smad2, Kruskal-Wallis test with Dunn’s multiple comparisons test for p-Smad3/Smad3). Data are presented as mean values +/− SEM.

Back to article page