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Gap junction reduction in cardiomyocytes following transforming growth factor-β treatment and Trypanosoma cruzi infection
- Source :
- Scopus-Elsevier, Memórias do Instituto Oswaldo Cruz, Volume: 104, Issue: 8, Pages: 1083-1090, Published: DEC 2009
- Publication Year :
- 2009
- Publisher :
- FapUNIFESP (SciELO), 2009.
-
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.
- Subjects :
- Adult
Male
Microbiology (medical)
Chagas disease
medicine.medical_specialty
transforming growth factor- β
Fluorescent Antibody Technique
Dioxoles
heart
030204 cardiovascular system & hematology
connexin 43
gap junction
Mice
03 medical and health sciences
0302 clinical medicine
Transforming Growth Factor beta
Fibrosis
Internal medicine
TGF beta signaling pathway
medicine
Animals
Humans
Myocyte
Chagas Disease
Myocytes, Cardiac
Trypanosoma cruzi
030304 developmental biology
0303 health sciences
Microscopy, Confocal
biology
Gap junction
Gap Junctions
Transforming growth factor beta
Middle Aged
medicine.disease
biology.organism_classification
Immunohistochemistry
3. Good health
Endocrinology
Connexin 43
Benzamides
biology.protein
Female
Receptors, Transforming Growth Factor beta
Transforming growth factor
Subjects
Details
- ISSN :
- 00740276
- Volume :
- 104
- Database :
- OpenAIRE
- Journal :
- Memórias do Instituto Oswaldo Cruz
- Accession number :
- edsair.doi.dedup.....1a679a8cd103293b072301bbd13ad5c1