TGF-β inhibitor therapy decreases fibrosis and stimulates cardiac improvement in a pre-clinical study of chronic Chagas’ heart disease
Fig 6
GW788388 treatment reverses MMP/TIMPs expression in the heart of mice chronically infected with T. cruzi after GW788388 treatment.
Mice were infected with the Colombian T. cruzi strain (102 parasites). Treatment with GW788388 started on 120 dpi until 150 dpi in two administration schemes: once a week (GW1x) and three times a week (GW3x). Non-infected (NI) mice were monitored as a control group. (A) MMP-9 mRNA levels, (B) MMP-2 mRNA levels relative to GAPDH levels from hearts of infected mice (2−ʎʎCt values, fold change) are plotted. (C) Representative zymography gel showing the gelatinolytic activity of MMP-9; Densitometric histogram of the mean values of detected gelatinolytic activities from (D) MMP-9 and (E) MMP-2. (F) Assessment of TIMP-1, TIMP-2 and TIMP-4 expression in the heart by Western blot analysis. Densitometric histograms of the normalized levels of TIMP-1 (G) TIMP-2 (H) and TIMP-4 (I) in relation to GAPDH are shown. Data represent mean± standard deviation of 6 mice per group in three independent experiments. Significant differences between infected and non-infected groups are indicated by $P<0.05 and $ $P<0.01, and differences between infected mice GW788388 treated or not are indicated by *P<0.05 and **P<0.01. n = 4–6 mice per group.