Figure 7.

Cardiac fibroblast specific USP10 deficiency abolished HSP47-mediated cardiac dysfunction and fibrogenesis in chronic ischemic hearts. (A–C) Con-miR1/133TS or HSP47-miR1/133TS was administered via tail vein injection to the USP10^fl/fl or USP10^fl/fl-Cre+ mice (dose 3 × 10⁸ PFU per mouse) for two weeks before surgery, and reperfused for 24 h. (A) Heart slices from indicated mice were stained with Evans blue and TTC at 24 h after myocardial IRI to determine (B, C) the area at risk (AAR) and infarcted region (IR). n = 6 per group. Scale bar = 0.5 cm. Differences were assessed by two-way ANOVA and Tukey's multiple comparison test. (D–H) Con-miR1/133TS or HSP47-miR1/133TS was administered via tail vein injection to the USP10^fl/fl or USP10^fl/fl-Cre+ mice (dose 3 × 10⁸ PFU per mouse) for two weeks before surgery, and continuously reperfused for 4 weeks. (D) Representative M-mode echocardiography was recorded. (E) LV ejection fraction (LVEF) was analyzed. n = 11–12 per group. Differences were assessed by two-way ANOVA and Tukey's multiple comparison test. (F, G) Representative Masson staining of heart slices from indicated mice and quantitative analyses of LV collagen volume. n = 6 per group. Scar bar = 80 μm. (H) Ubiquitination of Smad4 was detected by immunoprecipitation in isolated cardiac fibroblasts. n = 4 independent experiments. Data are presented as the mean ± SEM, with each point representing a mouse.