Fig. 4

Treatment with a soluble guanylate cyclase (sGC) stimulator improved esophageal and intestinal hyperproliferative and prefibrotic response. a Schematic representation of the experimental protocol. Osmotic pumps containing 200 μL of BLM (125 mg/kg) or NS were implanted on day 0. Pumps were removed on day 7. Mice were then treated with an oral sGC stimulator, BAY 63-2521, (10 mg/kg) (BLM + sGC group) or DMSO (BLM group) from day 14 to day 42, and then sacrificed on day 42 (6 w). b Body weight change from day 0 to day 42 in C57BL/6 mice. The body weight change was calculated as [(body weight on day 42) − (body weight on day 0)] × (body weight on day 0)⁻¹ × 100 (%) (n = 6–10 mice per group). c, d Representative histology of esophagus (c) and intestine (d) stained with MT at × 40 magnification. e, f The thickness (lamina–muscularis mucosa distance) of fibrosis in the esophagus (e) and intestine (f) fibrotic tissues stained with MT (n = 6–10 mice per group). g, h Soluble collagen production in the esophagus (g) and intestine (h) in NS-, BLM-, and BLM plus sGC stimulator-treated mice (n = 6–10 mice per group). i, j Representative histology of immunostaining with anti-αSMA and anti-PCNA antibodies in NS-, BLM-, and BLM plus sGC stimulator-treated mice (n = 6–10 mice per group) in the esophagus (i) and intestine (j). k The area stained positive for anti-αSMA antibody in the esophagus. l The thickness of αSMA-positive area in intestine. m, n The number of PCNA-positive cell in the esophagus (m) and intestine (n) (c, i the straight line represents 100 μm. d, j the straight line represents 200 μm). Bars represent mean + SD. *P < 0.05, **P < 0.01; one-way ANOVA, Tukey’s multiple comparison test. sGC, soluble guanylate cyclase; DMSO, dimethyl sulfoxide; PCNA, proliferating cell nuclear antigen