title: TGF-β receptor type II costameric localization in cardiomyocytes and host cell TGF-β response is disrupted by Trypanosoma cruzi infection.
abstract: 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.
authors.affiliation: Laboratório de Ultraestrutura Celular,Fundação Oswaldo Cruz,Av. Brasil 4365,Pav. Carlos Chagas 3° andar,Rio de Janeiro,Brazil.
authors.forename: Claudia Magalhães
authors.initials: CM
authors.lastname: Calvet
authors.affiliation: Laboratório de Ultraestrutura Celular,Fundação Oswaldo Cruz,Av. Brasil 4365,Pav. Carlos Chagas 3° andar,Rio de Janeiro,Brazil.
authors.forename: Tatiana Araújo
authors.initials: TA
authors.lastname: Silva
authors.affiliation: Laboratório de Ultraestrutura Celular,Fundação Oswaldo Cruz,Av. Brasil 4365,Pav. Carlos Chagas 3° andar,Rio de Janeiro,Brazil.
authors.forename: Tatiana Galvão
authors.initials: TG
authors.lastname: DE Melo
authors.affiliation: Laboratório de Inovações em Terapias,Ensino e Bioprodutos, Instituto Oswaldo Cruz,FIOCRUZ,Av. Brasil 4365,Manguinhos,Rio de Janeiro,RJ 21040-360,Brazil.
authors.forename: Tânia Cremonini
authors.initials: TC
authors.lastname: DE Araújo-Jorge
authors.affiliation: Laboratório de Ultraestrutura Celular,Fundação Oswaldo Cruz,Av. Brasil 4365,Pav. Carlos Chagas 3° andar,Rio de Janeiro,Brazil.
authors.forename: Mirian Claudia DE Souza
authors.initials: MC
authors.lastname: Pereira
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000503:physiopathology*; D054974:Costameres / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006790:Host-Parasite Interactions / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000469:parasitology / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000502:physiology
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: Cardiomyocytes; T. cruzi; TGF-β; TGF-β receptor type II; costameres