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TGF-β receptor type II costameric localization in cardiomyocytes and host cell TGF-β response is disrupted by Trypanosoma cruzi infection

Published online by Cambridge University Press:  21 March 2016

CLAUDIA MAGALHÃES CALVET ,
TATIANA ARAÚJO SILVA ,
TATIANA GALVÃO DE MELO ,
TÂNIA CREMONINI DE ARAÚJO-JORGE  and
MIRIAN CLAUDIA DE SOUZA PEREIRA
CLAUDIA MAGALHÃES CALVET*
Affiliation:
Laboratório de Ultraestrutura Celular, Fundação Oswaldo Cruz, Av. Brasil 4365, Pav. Carlos Chagas 3° andar, Rio de Janeiro, Brazil
TATIANA ARAÚJO SILVA
Affiliation:
Laboratório de Ultraestrutura Celular, Fundação Oswaldo Cruz, Av. Brasil 4365, Pav. Carlos Chagas 3° andar, Rio de Janeiro, Brazil
TATIANA GALVÃO DE MELO
Affiliation:
Laboratório de Ultraestrutura Celular, Fundação Oswaldo Cruz, Av. Brasil 4365, Pav. Carlos Chagas 3° andar, Rio de Janeiro, Brazil
TÂNIA CREMONINI DE ARAÚJO-JORGE
Affiliation:
Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ 21040-360, Brazil
MIRIAN CLAUDIA DE SOUZA PEREIRA
Affiliation:
Laboratório de Ultraestrutura Celular, Fundação Oswaldo Cruz, Av. Brasil 4365, Pav. Carlos Chagas 3° andar, Rio de Janeiro, Brazil
*
*Corresponding author: Laboratório de Ultraestrutura Celular, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, Manguinhos 21040-360 Rio de Janeiro, RJ, Brazil. Phone: +5521 25621027. E-mail: cmcalvet@ioc.fiocruz.br
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Summary

Transforming growth factor beta (TGF-β) cytokine is involved in Chagas disease establishment and progression. Since Trypanosoma cruzi can modulate host cell receptors, we analysed the TGF-β receptor type II (TβRII) expression and distribution during T. cruzi – cardiomyocyte interaction. TβRII immunofluorescent staining revealed a striated organization in cardiomyocytes, which was co-localized with vinculin costameres and enhanced (38%) after TGF-β treatment. Cytochalasin D induced a decrease of 45·3% in the ratio of cardiomyocytes presenting TβRII striations, demonstrating an association of TβRII with the cytoskeleton. Western blot analysis showed that cytochalasin D significantly inhibited Smad 2 phosphorylation and fibronectin stimulation after TGF-β treatment in cardiomyocytes. Trypanosoma cruzi infection elicited a decrease of 79·8% in the frequency of cardiomyocytes presenting TβRII striations, but did not interfere significantly in its expression. In addition, T. cruzi-infected cardiomyocytes present a lower response to exogenous TGF-β, showing no enhancement of TβRII striations and a reduction of phosphorylated Smad 2, with no significant difference in TβRII expression when compared to uninfected cells. Together, these results suggest that the co-localization of TβRII with costameres is important in activating the TGF-β signalling cascade, and that T. cruzi-derived cytoskeleton disorganization could result in altered or low TGF-β response in infected cardiomyocytes.

Keywords

CardiomyocytesT. cruziTGF-βTGF-β receptor type IIcostameres
Type
Research Article
Information
Parasitology , Volume 143 , Issue 6 , May 2016 , pp. 704 - 715
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Copyright
Copyright © Cambridge University Press 2016 

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