CERBAN FABIO MARCELO
Congresos y reuniones científicas
Título:
Trypanosoma cruzi infection induces Slug expression in heart during cardiac remodeling
Autor/es:
XIMENA VOLPINI; BAIGORRÍ, RUTH ELIANA; BRUGO MARIA BELEN; LAUTARO NATALI; CERBAN F; CRISTINA MOTRAN; MUSRI MELINA
Reunión:
Congreso; Reunión de la Sociedad Argentina de Investigación Clínica; 2019
Resumen:
Chagas disease is caused by Trypanosoma cruzi infection. Chronic cardiac manifestation (CCC) is consequence of a cardiovascular remodeling (CR) process that elicit a dilated cardiomyopathy that can trigger heart failure. This process starts in heart and vessels during the acute phase of the infection, but the molecular mechanisms are poorly understood. We reported that inhibition of Wnt proteins reduces CCC severity in BALB/c mice. Despite smooth muscle cells (SMC) dedifferentiation and fibroblast (Fb) differentiation into myofibroblasts play an important role in CR, little is known about their contribution to this progression. Slug is a transcription factor crucial during development and pathogenesis. Our group demonstrated that Slug is associated with vascular remodeling and promotes SMC dedifferentiation. We also recently observed that in vitro TGF-β treatment of SMC and Fb promotes Slug downregulation. In this work, we tested the hypothesis that Slug is involved in CR process during T. cruzi infection. Consequently, we aimed to determine Slug expression in heart during acute and chronic T. cruzi infection in absence and presence of Wnt proteins secretion inhibition. We also evaluated the presence of myofibroblasts in heart. BALB/c mice were infected with 1000 tripomastigotes and Slug was determined in hearts by q-PCR at different days post-infection (d pi). During acute phase of infection, a gradual upregulation of Slug that became statistically significant after 23 d pi respect to non-infected mice was observed (p=0.0277). The expression of Slug remained upregulated in heart (p=0.0330) during chronic phase of infection (180 d pi). Interestingly mice treated with a Wnt proteins secretion inhibitor (IWP-L6) increased TGF-β levels, partially blocked Slug upregulation and increased the number of myofibroblast in heart. Our results indicate that Slug could be involved in the regulation of CR during T. cruzi infection, probably by modulating SMC and Fb phenotype.