Key result
In T. cruzi-infected cardiac fibroblasts, TGF-β treatment reduced PS2 and increased p-p38 and p-c-Jun levels, suggesting these pathways participate in fibrosis regulation.
Why the study?
To determine the regulatory mechanisms of transforming growth factor beta in driving inflammation and fibrosis in cardiac and skeletal muscle during Chagas disease.
In T. cruzi-infected cardiac fibroblasts, TGF-β mediates fibrosis regulation potentially through p38 and c-Jun pathways rather than canonical SMAD signaling.
TGF-β may regulate fibrosis via p38/c-Jun in T. cruzi fibroblast models; hypothesis-generating and requires in vivo validation before any clinical consideration.
Transforming growth factor beta (TGF-β) is a determinant for inflammation and fibrosis in cardiac and skeletal muscle in Chagas disease. To determine its regulatory mechanisms, we investigated the response of T. cruzi-infected cardiomyocytes (CM), cardiac fibroblasts (CF) and L6E9 skeletal myoblasts to TGF-β. Cultures of CM, CF and L6E9 were infected with T. cruzi (Y strain) and treated with TGF-β (1–10 ng/mL, 1h or 48 h). Fibronectin (FN) distribution was analyzed by immunofluorescence and Western blot (WB). Phosphorylated SMAD2 (PS2), phospho-p38 (p-p38), and phospho-c-Jun (p-c-Jun) signaling were evaluated by WB. CF and L6E9 showed an increase in FN from 1 ng/mL of TGF-β, while CM displayed FN modulation only after 10 ng/mL treatment. CF and L6E9 showed higher PS2 levels than CM, while p38 is less stimulated in CF than CM and L6E9. After T. cruzi infection, localized FN disorganization was observed in infected CF and L6E9. T. cruzi induced an increase in FN in CF cultures, mainly in uninfected cells. Infected CF cultures treated with TGF-β showed a reduction in PS2 and an increase in p-p38 and p-c-Jun levels. Our data suggest that p38 and c-Jun pathways may be participating in the fibrosis regulatory process mediated by TGF-β after T. cruzi infection.
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Silva et al. (2019) studied Chagas disease. TGF-β treatment and T. cruzi infection vs. Untreated/uninfected cells was evaluated on Fibronectin distribution and signaling pathway activation (PS2, p-p38, p-c-Jun). In T. cruzi-infected cardiac fibroblasts, TGF-β treatment reduced PS2 and increased p-p38 and p-c-Jun levels, suggesting these pathways participate in fibrosis regulation.
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