Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/46757 |
Resumo: | Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador 41253-190, Brazil; carolina.nonaka@hsr.com.br (C.K.V.N.); luaragao@gmail.com (L.d.A.F); katia.nsilva@hsr.com.br (K.N.S.); brunoparedes@gmail.com (B.D.P); brunosolanosouza@gmail.com (B.S.d.F.S.) 2 Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil; gabrielalouise.sampaio@gmail.com (G.L.S.); brunorrcavalcante@gmail.com (B.R.C); ricardo_khouri@hotmail.com (R.K.); fgtorres18@gmail.com (F.G.T); calcio0303@hotmail.com (C.S.M); souza.emanuelle@hotmail.com (E.d.S.S); carolthemacedo@gmail.com (C.T.M.); viny_rocha@hotmail.com (V.P.C.R); ricardoribeiro1941@gmail.com (R.R.d.S.) 3 D’Or Institute for Research and Education (IDOR), Rio de Janeiro 20000-000, Brazil 4 Senai Institute of Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador 41253-190, Brazil 5 Department of Cardiology, São Rafael Hospital, Salvador 41253-190, Brazil 6 Department of Clinical Genetics, University Hospital of Southern Denmark-Vejle, 7100 Vejle, Denmark; silvia.rogatto2@gmail.com |
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Nonaka, Carolina Kymie VasquesSampaio, Gabriela LouiseFrança, Luciana de AragãoCavalcante, Bruno RaphaelSilva, Katia NunesCunha, Antonio Ricardo KhouriTorres, Felipe GuimarãesMeira, Cassio SantanaSantos, Emanuelle de SouzaMacedo, Carolina ThéParedes, Bruno DiazRocha, Vinicius Pinto CostaRogatto, Silvia ReginaSantos, Ricardo Ribeiro dosSouza, Bruno Solano de FreitasSoares, Milena Botelho Pereira2021-04-19T12:44:44Z2021-04-19T12:44:44Z2021NONAKA, Carolina Kymie Vasques et al. Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease. International Journal of Molecular Sciences, v. 22, 2021.1661-6596https://www.arca.fiocruz.br/handle/icict/4675710.3390/ijms22073307Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador 41253-190, Brazil; carolina.nonaka@hsr.com.br (C.K.V.N.); luaragao@gmail.com (L.d.A.F); katia.nsilva@hsr.com.br (K.N.S.); brunoparedes@gmail.com (B.D.P); brunosolanosouza@gmail.com (B.S.d.F.S.) 2 Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil; gabrielalouise.sampaio@gmail.com (G.L.S.); brunorrcavalcante@gmail.com (B.R.C); ricardo_khouri@hotmail.com (R.K.); fgtorres18@gmail.com (F.G.T); calcio0303@hotmail.com (C.S.M); souza.emanuelle@hotmail.com (E.d.S.S); carolthemacedo@gmail.com (C.T.M.); viny_rocha@hotmail.com (V.P.C.R); ricardoribeiro1941@gmail.com (R.R.d.S.) 3 D’Or Institute for Research and Education (IDOR), Rio de Janeiro 20000-000, Brazil 4 Senai Institute of Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador 41253-190, Brazil 5 Department of Cardiology, São Rafael Hospital, Salvador 41253-190, Brazil 6 Department of Clinical Genetics, University Hospital of Southern Denmark-Vejle, 7100 Vejle, Denmark; silvia.rogatto2@gmail.comBahia State Foundation for Research (FAPESB) and Instituto Nacional de Ciência e Tecnologia (INCT REGENERA; 465656/2014-5)."Múltipla ver em Notas"Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), remains a serious public health problem for which there is no effective treatment in the chronic stage. Intense cardiac fibrosis and inflammation are hallmarks of chronic Chagas disease cardiomyopathy (CCC). Previously, we identified upregulation of circulating and cardiac miR-21, a pro-fibrotic microRNA (miRNA), in subjects with CCC. Here, we explored the potential role of miR-21 as a therapeutic target in a model of chronic Chagas disease. PCR array-based 88 microRNA screening was performed in heart samples obtained from C57Bl/6 mice chronically infected with T. cruzi and serum samples collected from CCC patients. MiR-21 was found upregulated in both human and mouse samples, which was corroborated by an in silico analysis of miRNA-mRNA target prediction. In vitro miR-21 functional assays (gainand loss-of-function) were performed in cardiac fibroblasts, showing upregulation of miR-21 and collagen expression upon transforming growth factor beta 1 (TGF 1) and T. cruzi stimulation, while miR-21 blockage reduced collagen expression. Finally, treatment of T. cruzi-infected mice with locked nucleic acid (LNA)-anti-miR-21 inhibitor promoted a significant reduction in cardiac fibrosis. Our data suggest that miR-21 is a mediator involved in the pathogenesis of cardiac fibrosis and indicates the pharmacological silencing of miR-21 as a potential therapeutic approach for CCC.engMDPImicroRNAsTrypanosoma cruziDoença de ChagasCardiomiopatiasFibroseCoraçãomicroRNATherapeutic targetChagas diseaseCardiomyopathyFibrosismiR-21Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Diseaseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/46757/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALNonaka, Carolina Kymie Vasques. Terapeutic....pdfNonaka, Carolina Kymie Vasques. 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| dc.title.pt_BR.fl_str_mv |
Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease |
| title |
Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease |
| spellingShingle |
Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease Nonaka, Carolina Kymie Vasques microRNAs Trypanosoma cruzi Doença de Chagas Cardiomiopatias Fibrose Coração microRNA Therapeutic target Chagas disease Cardiomyopathy Fibrosis miR-21 |
| title_short |
Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease |
| title_full |
Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease |
| title_fullStr |
Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease |
| title_full_unstemmed |
Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease |
| title_sort |
Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease |
| author |
Nonaka, Carolina Kymie Vasques |
| author_facet |
Nonaka, Carolina Kymie Vasques Sampaio, Gabriela Louise França, Luciana de Aragão Cavalcante, Bruno Raphael Silva, Katia Nunes Cunha, Antonio Ricardo Khouri Torres, Felipe Guimarães Meira, Cassio Santana Santos, Emanuelle de Souza Macedo, Carolina Thé Paredes, Bruno Diaz Rocha, Vinicius Pinto Costa Rogatto, Silvia Regina Santos, Ricardo Ribeiro dos Souza, Bruno Solano de Freitas Soares, Milena Botelho Pereira |
| author_role |
author |
| author2 |
Sampaio, Gabriela Louise França, Luciana de Aragão Cavalcante, Bruno Raphael Silva, Katia Nunes Cunha, Antonio Ricardo Khouri Torres, Felipe Guimarães Meira, Cassio Santana Santos, Emanuelle de Souza Macedo, Carolina Thé Paredes, Bruno Diaz Rocha, Vinicius Pinto Costa Rogatto, Silvia Regina Santos, Ricardo Ribeiro dos Souza, Bruno Solano de Freitas Soares, Milena Botelho Pereira |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Nonaka, Carolina Kymie Vasques Sampaio, Gabriela Louise França, Luciana de Aragão Cavalcante, Bruno Raphael Silva, Katia Nunes Cunha, Antonio Ricardo Khouri Torres, Felipe Guimarães Meira, Cassio Santana Santos, Emanuelle de Souza Macedo, Carolina Thé Paredes, Bruno Diaz Rocha, Vinicius Pinto Costa Rogatto, Silvia Regina Santos, Ricardo Ribeiro dos Souza, Bruno Solano de Freitas Soares, Milena Botelho Pereira |
| dc.subject.other.pt_BR.fl_str_mv |
microRNAs Trypanosoma cruzi Doença de Chagas Cardiomiopatias Fibrose Coração |
| topic |
microRNAs Trypanosoma cruzi Doença de Chagas Cardiomiopatias Fibrose Coração microRNA Therapeutic target Chagas disease Cardiomyopathy Fibrosis miR-21 |
| dc.subject.en.pt_BR.fl_str_mv |
microRNA Therapeutic target Chagas disease Cardiomyopathy Fibrosis miR-21 |
| description |
Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador 41253-190, Brazil; carolina.nonaka@hsr.com.br (C.K.V.N.); luaragao@gmail.com (L.d.A.F); katia.nsilva@hsr.com.br (K.N.S.); brunoparedes@gmail.com (B.D.P); brunosolanosouza@gmail.com (B.S.d.F.S.) 2 Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil; gabrielalouise.sampaio@gmail.com (G.L.S.); brunorrcavalcante@gmail.com (B.R.C); ricardo_khouri@hotmail.com (R.K.); fgtorres18@gmail.com (F.G.T); calcio0303@hotmail.com (C.S.M); souza.emanuelle@hotmail.com (E.d.S.S); carolthemacedo@gmail.com (C.T.M.); viny_rocha@hotmail.com (V.P.C.R); ricardoribeiro1941@gmail.com (R.R.d.S.) 3 D’Or Institute for Research and Education (IDOR), Rio de Janeiro 20000-000, Brazil 4 Senai Institute of Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador 41253-190, Brazil 5 Department of Cardiology, São Rafael Hospital, Salvador 41253-190, Brazil 6 Department of Clinical Genetics, University Hospital of Southern Denmark-Vejle, 7100 Vejle, Denmark; silvia.rogatto2@gmail.com |
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NONAKA, Carolina Kymie Vasques et al. Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease. International Journal of Molecular Sciences, v. 22, 2021. |
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https://www.arca.fiocruz.br/handle/icict/46757 |
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1661-6596 |
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10.3390/ijms22073307 |
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NONAKA, Carolina Kymie Vasques et al. Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease. International Journal of Molecular Sciences, v. 22, 2021. 1661-6596 10.3390/ijms22073307 |
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