Fig 2: P2X4 receptor potentiation ameliorates dextran sodium sulphate (DSS)-induced colitis. (A) Experimental design of the role of IVM in colitis in mice. See materials and methods for details. (B) Body weight change. (C) Representative images of bloody diarrhea. (D) Disease activity index (DAI) score. (E) Representative pictures of the gross colonic appearance. (F) Colon length is shown as a chart. (G) Representative microscopic pictures of hematoxylin and eosin (H&E) and Periodic Acid-Schiff (PAS) staining (original × magnification 40). (H) Changes in colonic section histopathological scores. (I) The number of PAS-positive cells per villus/crypt. Results are expressed as mean ± SEM (B, D, F, H, I). p-values were calculated using a two-way analysis of variance (ANOVA) test, *p < .05; **p < .01; ***p < .001. (Control, n = 4; DSS, n = 7; DSS+2 mg IVM, n = 8; DSS+5 mg IVM, n = 8). Control, Con.

Fig 3: P2rx4 deficiency activates MAPK signalling and exacerbates inflammatory responses. (A) Interleukin (IL)‐6 and interferon (IFN)‐γ concentrations in the plasma. (B) IL‐6, IL‐1β, IFN‐γ and TNF‐α concentrations in the colonic tissue lysate. (C) Effect of P2rx4 on MAPK‐related protein expression in mice with colitis. Representative gels were shown, and data were summarized from three independent experiments and analyzed using one‐way analysis of variance (ANOVA) followed by Tukey's test. (WT, n = 4; P2rx4−/− , n = 4; WT + dextran sodium sulphate (DSS), n = 7; P2rx4−/− +DSS, n = 7). Results are expressed as mean ± SEM. *p < .05; **p < .01.

Fig 4: P2rx4 ablation exhibits increased susceptibility to dextran sodium sulphate (DSS)-induced colitis. (A) Experimental design of DSS-induced colitis. See materials and methods for details. (B) Body weight change. (C) Representative images of bloody diarrhoea. (D) Disease activity index (DAI) score. (E) Representative pictures of gross colonic appearance. (F) Colon length is shown as a chart. (G) Representative microscopic pictures of hematoxylin and eosin (H&E) staining and Periodic Acid-Schiff (PAS) staining (original × magnification 40). (H) Changes in colonic section histopathological scores. (I) The number of PAS-positive cells per crypt. Results are expressed as mean ± SEM (B, D, F, H, I). p-Values were calculated using a two-way analysis of variance (ANOVA) test, *p < .05; **p < .01. (WT, n = 4; P2rx4-/- , n = 4; WT+DSS, n = 7; P2rx4-/- +DSS, n = 7).

Fig 5: Gut microbiota from P2rx4-/- mice aggravates dextran sodium sulphate (DSS)-induced colitis. (A) Design of the cohousing experiment. See materials and methods for details. (B) Body weight change. (C) Representative images of bloody diarrhoea. (D) Disease activity index (DAI) score. (E) Representative pictures of the gross colonic appearance. (F) Colon length is shown as a chart. (G) Representative microscopic pictures of hematoxylin and eosin (H&E) staining (original × magnification 40). (H) Changes in colonic section histopathological scores. Results are expressed as mean ± SEM (B, D, F, H). p-values were calculated using a two-way analysis of variance (ANOVA) test, *p < .05; **p < .01; ***p < .001. (Cohoused: WT, n = 8; P2rx4-/- , n = 8; No-Cohoused: WT, n = 8; P2rx4-/- , n = 8).