{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T23:48:01Z","timestamp":1771026481524,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bahia State Foundation for Research","award":["PET0029\/2013"],"award-info":[{"award-number":["PET0029\/2013"]}]},{"DOI":"10.13039\/501100007762","name":"Instituto Nacional de Ci\u00eancia e Tecnologia Translacional em Medicina","doi-asserted-by":"publisher","award":["INCT 465656\/2014-5"],"award-info":[{"award-number":["INCT 465656\/2014-5"]}],"id":[{"id":"10.13039\/501100007762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 (gain-and loss-of-function) were performed in cardiac fibroblasts, showing upregulation of miR-21 and collagen expression upon transforming growth factor beta 1 (TGF\u03b21) 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.<\/jats:p>","DOI":"10.3390\/ijms22073307","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T15:42:19Z","timestamp":1616600539000},"page":"3307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Carolina Kymie Vasques","family":"Nonaka","sequence":"first","affiliation":[{"name":"Center for Biotechnology and Cell Therapy, S\u00e3o Rafael Hospital, Salvador 41253-190, Brazil"},{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro 20000-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela Louise","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"Senai Institute of Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador 41253-190, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana","family":"de Arag\u00e3o Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Cell Therapy, S\u00e3o Rafael Hospital, Salvador 41253-190, Brazil"},{"name":"D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro 20000-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno Raphael","family":"Cavalcante","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia Nunes","family":"Silva","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Cell Therapy, S\u00e3o Rafael Hospital, Salvador 41253-190, Brazil"},{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro 20000-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Khouri","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0506-8568","authenticated-orcid":false,"given":"Felipe Guimar\u00e3es","family":"Torres","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassio Santana","family":"Meira","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"Senai Institute of Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador 41253-190, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuelle","family":"de Souza Santos","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"Senai Institute of Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador 41253-190, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5129-7639","authenticated-orcid":false,"given":"Carolina Th\u00e9","family":"Macedo","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"Senai Institute of Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador 41253-190, Brazil"},{"name":"Department of Cardiology, S\u00e3o Rafael Hospital, Salvador 41253-190, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno Diaz","family":"Paredes","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Cell Therapy, S\u00e3o Rafael Hospital, Salvador 41253-190, Brazil"},{"name":"D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro 20000-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5309-5950","authenticated-orcid":false,"given":"Vinicius Pinto Costa","family":"Rocha","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"Senai Institute of Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador 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