eprintid: 1311106 rev_number: 37 eprint_status: archive userid: 608 dir: disk0/01/31/11/06 datestamp: 2011-06-19 20:50:53 lastmod: 2021-11-07 00:40:08 status_changed: 2013-11-14 11:59:48 type: article metadata_visibility: show item_issues_count: 0 creators_name: Waghabi, MC creators_name: Coutinho-Silva, R creators_name: Feige, JJ creators_name: Higuchi, MD creators_name: Becker, D creators_name: Burnstock, G creators_name: de Araujo-Jorge, TC title: Gap junction reduction in cardiomyocytes following transforming growth factor- beta treatment and Trypanosoma cruzi infection ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 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 note: All the contents of Memórias do Instituto Oswaldo Cruz journal, except where otherwise noted, is licensed under a Creative Commons Attribution License (CC-BY). 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. date: 2009-12 publisher: FUNDACO OSWALDO CRUZ official_url: http://www.scielo.br/scielo.php?pid=0074-0276&script=sci_serial vfaculties: VFLS oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Article verified: verified_batch elements_source: Web of Science elements_id: 318565 language_elements: EN lyricists_name: Becker, David lyricists_name: Burnstock, Geoffrey lyricists_id: DLBEC91 lyricists_id: GBURN46 full_text_status: public publication: Memórias do Instituto Oswaldo Cruz volume: 104 number: 8 pagerange: 1083-1090 issn: 0074-0276 citation: 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. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1311106/1/04.pdf