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

Int J Mol Sci. 2019 Sep 29;20(19):4836. doi: 10.3390/ijms20194836.

Abstract

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 Trypanosoma 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, 1 h 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 was less stimulated in CF than CM and L6E9. T. cruzi infection resulted in localized FN disorganization in 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.

Keywords: SMAD2; TGF-β; Trypanosoma cruzi; c-Jun; extracellular matrix; heart fibrosis; p38 MAPK; signaling pathways.

MeSH terms

  • Animals
  • Biomarkers
  • Cell Line
  • Cells, Cultured
  • Chagas Disease / metabolism*
  • Chagas Disease / parasitology*
  • Extracellular Matrix / metabolism*
  • Fibroblasts / metabolism
  • Fibronectins / metabolism
  • Host-Pathogen Interactions*
  • Myocytes, Cardiac / metabolism
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism*
  • Trypanosoma cruzi / physiology*

Substances

  • Biomarkers
  • Fibronectins
  • Transforming Growth Factor beta