Waghabi, MC;
Coutinho-Silva, R;
Feige, JJ;
Higuchi, MD;
Becker, D;
Burnstock, G;
de Araujo-Jorge, TC;
(2009)
Gap junction reduction in cardiomyocytes following transforming growth factor- beta treatment and Trypanosoma cruzi infection.
Memórias do Instituto Oswaldo Cruz
, 104
(8)
pp. 1083-1090.
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Abstract
Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-beta (TGF-beta). This cytokine increases during Trypanosoma cruzi infection, modulating fibrosis and the parasite cell cycle. We studied Cx43 expression in cardiomyocytes exposed or not to TGF-beta T. cruzi, or SB-431542, an inhibitor of TGF-beta receptor type I (ALK-5). Cx43 expression was also examined in hearts with dilated cardiopathy from chronic Chagas disease patients, in which TGF-beta signalling had been shown previously to be highly activated. We demonstrated that TGF-beta treatment induced disorganised gap junctions in non-infected cardiomyocytes, leading to a punctate, diffuse and non-uniform Cx43 staining. A similar pattern was detected in T. cruzi-infected cardiomyocytes concomitant with high TGF-beta secretion. Both results were reversed if the cells were incubated with SB-431542. Similar tests were performed using human chronic chagasic patients and we confirmed a down-regulation of Cx43 expression, an altered distribution of plaques in the heart and a significant reduction in the number and length of Cx43 plaques, which correlated negatively with cardiomegaly. We conclude that elevated TGF-beta levels during T. cruzi infection promote heart fibrosis and disorganise gap junctions, possibly contributing to abnormal impulse conduction and arrhythmia that characterise severe cardiopathy in Chagas disease.
| Type: | Article |
|---|---|
| Title: | Gap junction reduction in cardiomyocytes following transforming growth factor- beta treatment and Trypanosoma cruzi infection |
| Open access status: | An open access version is available from UCL Discovery |
| Publisher version: | http://www.scielo.br/scielo.php?pid=0074-0276&scri... |
| Language: | English |
| Additional information: | All the contents of Memórias do Instituto Oswaldo Cruz journal, except where otherwise noted, is licensed under a Creative Commons Attribution License (CC-BY). |
| Keywords: | gap junction, heart, Chagas disease, transforming growth factor-beta, connexin 43, PARASITE CYCLE COMPLETION, CHAGAS HEART-DISEASE, INTERCELLULAR COMMUNICATION, VENTRICULAR MYOCARDIUM, CONNEXIN43 EXPRESSION, DOWN-REGULATION, MESSENGER-RNA, P2 RECEPTORS, TGF-BETA, IN-VITRO |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1311106 |
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