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Figure 1 | Skeletal Muscle

Figure 1

From: Angiotensin II type 1 receptor antagonists alleviate muscle pathology in the mouse model for laminin-α2-deficient congenital muscular dystrophy (MDC1A)

Figure 1

L-158809 lowered angiotensin II receptor type 1 (AT1) -mediated transforming growth factor (TGF)-β levels in the muscles of dyW/dyWmice. (A) AT1-mediated TGF-β levels were increased in muscles of dyW/dyWmice and decreased after L-158809 administration. Triceps cross-sections of dyW/dyWmice showed expression of TGF-β (green) and periostin (green), and nuclear accumulation of pSmad2/3 (green), which is a downstream target of AT1. Oral L-158809 treatment of dyW/dyWmice (dyW-L158) reduced expression of all three proteins. Nuclei were visualized with 4",6"-diamidino-2-phenylindole hydrochloride (DAPI) (blue). (B) Western blotting analysis of triceps muscles confirmed increased protein expression levels of periostin (75 to 85 kDa) and TGF-β (12 kDa, reduced) in dyW/dyWmice as well as the reduction after L-158809 treatment. β-actin was used as a loading control. (C) The number of pSmad2/3-positive nuclei was more than 25-fold increased in cross-sections of dyW/dyWmuscle compared with wild-type (WT) muscles, and was significantly reduced by L-158809 to levels 2-fold (triceps) and 2.6-fold (diaphragm) those of WT mice, which was not significant (n ≥ 4). (D) Quantitative real-time PCR showed an increase of approximately 3.5-fold in TGF-β1 mRNA levels in both dyW/dyWtriceps and diaphragm muscles, which was reduced to nearly WT levels by L-158809 (n ≥ 4). (E) Thrombospondin-1 (green) was increased in both triceps and diaphragm muscles of dyW/dyWmice, and was minimized by L-158809 administration. All values represent the mean ± SEM. One-way ANOVA: **P ≤ 0.001; * P ≤ 0.05; n.s. (non-significant) P > 0.05. Scale bar = 50 μm.

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