Fig. 6

Effects of iguratimod in skin grafts from naïve SSc patients. A Clinical characteristics of the three SSc patients. All patients were treatment naïve. Disease duration was measured from the onset of the first non-Raynaud symptoms attributable to SSc. Interstitial lung disease was diagnosed by high-resolution CT. Pulmonary arterial hypertension was screened by ultrasound. (B Each lesional skin tissue from the patients was transplanted subcutaneously into two irradiated nude mice. The grafts were injected with 0.1 mg/ml iguratimod or vehicle every day for 5 weeks. C Sirius red staining for each graft. The red parts represent collagen and the green parts represent total protein. Scale bars = 1 mm. D The collagen content of each skin tissue was quantified by eluting the dye and colorimetric assay. E Representative images of EGR1 and TGFβ staining. Scale bar = 125 μm. F The proportion of TGFβ ( +) and EGR1 ( +) fibroblasts in each mm². G GSEA of representative gene ensembles associated with ECM production. Data from RNA-Seq of all skin grafts treated with or without iguratimod. H Plot of FDR versus the NES based upon GSEA of each possible gene ensemble. * represents ECM production associated gene ensembles. D and F Mann–Whitney U test was used for statistical analyses. *, 0.05 > P > 0.01. mRSS, the modified Rodnan skin score; ILD, interstitial lung disease; DU, digital ulcer; PAH, pulmonary arterial hypertension; ACA, anti-Centromere antibody; IGU, iguratimod; NES, normalized enrichment score; FDR, false discovery rate