Pharmacological Inhibition of Transforming Growth Factor β Signaling Decreases Infection and Prevents Heart Damage in Acute Chagas' Disease
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Chagas' disease induced by Trypanosoma cruzi infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. We previously reported that transforming growth factor β (TGF-β) is implicated in several regulatory aspects of T . cruzi invasion and growth and in host tissue fibrosis. This prompted us to evaluate the therapeutic action of an inhibitor of TGF-β signaling (SB-431542) administered during the acute phase of experimental Chagas' disease. Male Swiss mice were infected intraperitoneally with 10 4 trypomastigotes of T . cruzi (Y strain) and evaluated clinically for the following 30 days. SB-431542 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that SB-431542 treatment was effective in protecting the cardiac conduction system. By 14 day postinfection, enzymatic biomarkers of tissue damage indicated that muscle injury was decreased by SB-431542 treatment, with significantly lower blood levels of aspartate aminotransferase and creatine kinase. In conclusion, inhibition of TGF-β signaling in vivo appears to potently decrease T . cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic agent for acute and chronic Chagas' disease that warrants further clinical exploration.
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In vivo pharmacological blockade of TGFβRI/II using SB431542 and losartan decreases Smad2/3 signaling in the peri-infarct tissue during the period of GDF activity after stroke.
“Furthermore, in vivo pharmacological blockade of TGFβRI/II using SB431542 and losartan19,20 decreases Smad2/3 signaling in the peri-infarct tissue (Supplementary Fig. 5) during the period of GDF activity after stroke.”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [20]
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References 37 · Cited by 66
- Authors
- Waghabi, M. C., de Souza, E. M., de Oliveira, G. M., Keramidas, M., Feige, J.-J., Araújo-Jorge, T. C., & Bailly, S.
- Affiliations
- Instituto Oswaldo Cruz (BR)
- Laboratório de Biologia Celular
- Institut National de la Santé et de la Recherche Médicale, U878, 17 rue des Martyrs, 38054 Grenoble
- Inserm (FR)
- Laboratório de Inovações em Terapias, Ensino e Bioprodutos
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2009-11
- Volume
- 53
- Issue
- 11
- Pages
- 4694-4701
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC2772341
- OpenAlex
- W2113729154
- Cited by
- 66
- References
- 37
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 3 · 2022: 9 · 2021: 1 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 1 · 2016: 7 · 2015: 3 · 2014: 5 · 2013: 1 · 2012: 11
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (publishedVersion, other-oa)
- Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
- Fundação Oswaldo Cruz
- Topics
- Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
- Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
- Keywords
- Chagas disease, Trypanosoma cruzi, TGF-beta inhibition, SB431542, acute infection, cardiac injury, cardiac conduction system, myocardial injury, parasitemia, host-parasite interactions, therapeutic target
- MeSH terms
- Receptor, Transforming Growth Factor-beta Type I, Animals, Benzamides, Bradycardia, Chagas Cardiomyopathy, Dioxoles, Male, Myocardium, Chagas Disease, Signal Transduction, Protein Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Parasitemia, Mice
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