Multicellular regulation of miR-196a-5p and miR-425-5 from adipose stem cell-derived exosomes and cardiac repair

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorOLIVEIRA, N. C. de Almeida
dc.contributor.authorNERI, E. A.
dc.contributor.authorSILVA, C. M.
dc.contributor.authorVALADãO, I. C.
dc.contributor.authorFONSECA-ALANIZ, M. H.
dc.contributor.authorZOGBI, C.
dc.contributor.authorLEVY, D.
dc.contributor.authorBYDLOWSKI, S. P.
dc.contributor.authorKRIEGER, J. E.
dc.date.accessioned2023-10-04T14:44:06Z
dc.date.available2023-10-04T14:44:06Z
dc.date.issued2022
dc.description.abstractCardiac transplantation of adipose-derived stem cells (ASC) modulates the post-myocardial infarction (post-MI) repair response. Biomolecules secreted or shuttled within extracellular vesicles, such as exosomes, may participate in the concerted response. We investigated the exosome’s microRNAs due to their capacity to fine-tune gene expression, potentially affecting the multicellular repair response. We profiled and quantified rat ASC-exosome miRNAs and used bioinformatics to select uncharacterized miRNAs down-regulated in post-MI related to cardiac repair. We selected and validated miR-196a-5p and miR-425-5p as candidates for the concerted response in neonatal cardiomyocytes, cardiac fibroblasts, endothelial cells, and macrophages using a high-content screening platform. Both miRNAs prevented cardiomyocyte ischemia-induced mitochondrial dysfunction and reactive oxygen species production, increased angiogenesis, and polarized macrophages toward the anti-inflammatory M2 immunophenotype. Moreover, miR-196a-5p reduced and reversed myofibroblast activation and decreased collagen expression. Our data provide evidence that the exosome-derived miR-196a-5p and miR-425-5p influence biological processes critical to the concerted multicellular repair response post-MI. © 2022 The Author(s).eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexScopus
dc.description.sponsorshipConselho Na-cional de Pesquisa
dc.description.sponsorshipCoordenac¸ ão de Aperfeic¸ oamento de Pessoal de Nível Superior
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP, (15/50216-5, 2013/17368-0, 2017/07024-3, 2017/17296-0)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES, (88887.643917/2021-00)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, (309179/2013-0, 441020/2018-6, INCT - 465586/2014-7)
dc.identifier.citationCLINICAL SCIENCE, v.136, n.17, p.1281-1301, 2022
dc.identifier.doi10.1042/CS20220216
dc.identifier.issn0143-5221
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/55889
dc.language.isoeng
dc.publisherPORTLAND PRESS LTDeng
dc.relation.ispartofClinical Science
dc.rightsopenAccesseng
dc.rights.holderCopyright PORTLAND PRESS LTDeng
dc.subject.otherarginase 1eng
dc.subject.othermicrornaeng
dc.subject.othermicrorna 196a 5peng
dc.subject.othermicrorna 425 5eng
dc.subject.otherprotein baxeng
dc.subject.otherprotein bcl 2eng
dc.subject.otherreactive oxygen metaboliteeng
dc.subject.otherunclassified drugeng
dc.subject.otheradipose derived stem celleng
dc.subject.otheradipose-derived mesenchymal stem celleng
dc.subject.otheradulteng
dc.subject.otherangiogenesiseng
dc.subject.otheranimal celleng
dc.subject.otheranimal experimenteng
dc.subject.otherarticleeng
dc.subject.otherbioinformaticseng
dc.subject.otherbone marrow derived macrophageeng
dc.subject.othercapillary endothelial celleng
dc.subject.othercardiac muscle celleng
dc.subject.othercell activationeng
dc.subject.othercell differentiationeng
dc.subject.othercell isolationeng
dc.subject.othercell metabolismeng
dc.subject.othercell proliferationeng
dc.subject.othercervical spine dislocationeng
dc.subject.othercontrolled studyeng
dc.subject.otherdisorders of mitochondrial functionseng
dc.subject.otherdown regulationeng
dc.subject.otherendothelium celleng
dc.subject.otherexosomeeng
dc.subject.otherfluorescence intensityeng
dc.subject.otherfluorescence microscopyeng
dc.subject.othergene expressioneng
dc.subject.othergene ontologyeng
dc.subject.otherheart fibroblasteng
dc.subject.otherheart transplantationeng
dc.subject.otherhigh content screeningeng
dc.subject.otherimmunofluorescenceeng
dc.subject.otherimmunophenotypingeng
dc.subject.otheringuinal fateng
dc.subject.othermaleeng
dc.subject.othermarker geneeng
dc.subject.othermitochondrial biogenesiseng
dc.subject.othermitochondrial dynamicseng
dc.subject.othermyofibroblasteng
dc.subject.othernonhumaneng
dc.subject.otherprimary cell cultureeng
dc.subject.otherprotein expressioneng
dc.subject.otherrateng
dc.subject.otherreal time polymerase chain reactioneng
dc.subject.othertarget celleng
dc.subject.othertubulogenesiseng
dc.subject.otherwestern blottingeng
dc.titleMulticellular regulation of miR-196a-5p and miR-425-5 from adipose stem cell-derived exosomes and cardiac repaireng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.author.externalOLIVEIRA, N. C. de Almeida:Laboratory of Genetics and Molecular Cardiology/LIM 13, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
hcfmusp.author.externalZOGBI, C.:Laboratory of Genetics and Molecular Cardiology/LIM 13, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
hcfmusp.citation.scopus10
hcfmusp.contributor.author-fmusphcELIDA ADALGISA NERI
hcfmusp.contributor.author-fmusphcCAIO MATEUS DA SILVA
hcfmusp.contributor.author-fmusphcIURI CORDEIRO VALADAO
hcfmusp.contributor.author-fmusphcMIRIAM HELENA FONSECA ALANIZ
hcfmusp.contributor.author-fmusphcDEBORA LEVY
hcfmusp.contributor.author-fmusphcSERGIO PAULO BYDLOWSKI
hcfmusp.contributor.author-fmusphcJOSE EDUARDO KRIEGER
hcfmusp.description.beginpage1281
hcfmusp.description.endpage1301
hcfmusp.description.issue17
hcfmusp.description.volume136
hcfmusp.origemSCOPUS
hcfmusp.origem.pubmed35894060
hcfmusp.origem.scopus2-s2.0-85137156225
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Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/InCor
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