FIGURE 2

Elevated TGF‐β signaling caused increased Nox4 expression and elevated oxidative stress in GO. (a) 1D11 treatment inhibited the Nox4 upregulation in Gorab^Prx1 mice (N = 5) (b) Representative images and (c) quantitation of Mitosox intensity in GO patient fibroblasts (N = 3–6) treated with TGF‐β inhibitor SB431542. (d) SB431542 reduced Nox4 expression in GO patient fibroblasts (N = 3–4). (e) Coculturing of control fibroblasts with GO patient fibroblasts caused upregulation of mitosox signal in the control fibroblasts, which can be prevented by SB431542 (N = 4–5). (f) Increased in mitosox signal in the bone marrow of tibiae of 4 weeks old Gorab^Prx1 (N = 4) in vivo. (g) Knockdown of gorab in zebrafish by TALEN resulted in upregulation of serpine1 and nox4 expression. (h) Representative picture and (i) quantitation of Mitosox positive cells by flow cytometry in gorab^TALEN zebrafish embryos. *p < 0.05, **p < 0.01, ns, no statistically significant difference (unpaired Welch's t‐test). Scale bar = 100 μm.