Differential Role of TGF-β in Extracellular Matrix Regulation During Trypanosoma cruzi-Host Cell Interaction

Area of Science:

• Cardiovascular Biology
• Parasitology
• Muscle Physiology

Background:

• Transforming growth factor beta (TGF-β) is implicated in inflammation and fibrosis in Chagas disease affecting cardiac and skeletal muscle.
• Understanding TGF-β regulatory mechanisms is crucial for developing therapeutic strategies.

Purpose of the Study:

• To investigate the cellular response of cardiomyocytes (CM), cardiac fibroblasts (CF), and skeletal myoblasts (L6E9) to TGF-β stimulation in the context of Trypanosoma cruzi infection.
• To elucidate the role of specific signaling pathways (SMAD2, p38, c-Jun) in TGF-β-mediated fibronectin modulation.

Main Methods:

• Primary cell cultures (CM, CF, L6E9) were infected with T. cruzi (Y strain) and treated with varying concentrations of TGF-β.
• Fibronectin (FN) distribution was assessed using immunofluorescence and Western blot.
• Key signaling proteins including phosphorylated SMAD2 (PS2), phospho-p38 (p-p38), and phospho-c-Jun (p-c-Jun) were analyzed via Western blot.

Main Results:

• TGF-β induced fibronectin (FN) expression in CF and L6E9 at lower concentrations than in CM.
• T. cruzi infection disorganized FN in CF and L6E9 and increased FN in CF, primarily in uninfected cells.
• Infected CF treated with TGF-β exhibited reduced PS2 and increased p-p38 and p-c-Jun signaling.

Conclusions:

• TGF-β differentially affects fibronectin expression in cardiac and skeletal muscle cells.
• The p38 and c-Jun signaling pathways appear to play a role in TGF-β-mediated fibrosis following T. cruzi infection.
• These findings provide insights into the molecular mechanisms underlying Chagas disease-related fibrosis.