Role of microRNA-21-loaded extracellular vesicles in liver-muscle intercommunication during Metabolic Dysfunction–associated Steatotic Liver Disease

Detalhes bibliográficos
Autor(a) principal: Rodrigues, José Alberto Correia Pereira
Data de Publicação: 2024
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Texto Completo: http://hdl.handle.net/10400.5/97781
Resumo: Tese de mestrado, Biologia Evolutiva e do Desenvolvimento, 2025, Universidade de Lisboa, Faculdade de Ciências
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spelling Role of microRNA-21-loaded extracellular vesicles in liver-muscle intercommunication during Metabolic Dysfunction–associated Steatotic Liver DiseaseComunicação fígado para músculoMASLDmiR-21SarcopeniaVesículas extracelularesTeses de mestrado - 2025Departamento de Biologia AnimalTese de mestrado, Biologia Evolutiva e do Desenvolvimento, 2025, Universidade de Lisboa, Faculdade de CiênciasMetabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, presenting a wide spectrum of metabolic dysregulation. However, its progression extends beyond the liver, affecting extrahepatic organs. In skeletal muscle, sarcopenia and myosteatosis are often associated with advanced MASLD. Previous studies showed that microRNA-21 (miR-21) continuously increases with MASLD progression in the liver, serum and skeletal muscle, while its ablation improves outcomes in animal models. In this work, we aimed to evaluate whether liver-derived extracellular vesicles (EVs) containing miR-21 contribute to skeletal muscle dysfunction in MASLD, using both a diet-induced MASLD mouse model and an in vitro model of hepatocyte-to-myotube communication. Mir21 whole-body knockout (WB-KO); Mir21 Alb-Cre KO (Alb-Cre-KO) and wildtype (WT) mice were fed a high-fat diet (HFD), with high fructose/glucose drinking water for 20 weeks or a standard diet. AML12-derived EVs were incubated with C2C12 myotubes for miR-21 assays and gene expression was evaluated by RT-qPCR. HFD mice displayed hepatic steatosis without muscle atrophy or changes in miR-21 levels. However, WB-KO mice showed increased levels of muscle regeneration factors Pax7 and Myod1, counteracting the decreases observed in WT HFD-fed mice. Additionally, Alb-Cre-KO HFD-fed mice exhibited reduced expression of atrophy-related gene Fbxo32 compared to WT HFD-fed mice. Hepatocyte miR-21 overexpression led to an increase in miR-21- loaded EVs, which subsequently elevated miR-21 expression in myotubes. This resulted in increased levels of genes associated with lipid metabolism, inflammation, muscle regeneration and atrophy, while decreasing levels of muscle growth inhibitor Myostatin. Notably, miR-21 inhibition in palmitic acidtreated hepatocytes reduced secreted miR-21 in EVs. However, myotube miR-21 expression remained unchanged after incubation. Overall, these findings suggest that miR-21 ablation promotes skeletal muscle regeneration and inhibits atrophy. The in vitro model highlighted the role of hepatocytes-derived miR-21-loaded EVs in inducing myotube dysfunction, closely resembling transcription profiles seen in MASLD-associated sarcopenia patients.Simão, André Daniel Lopes, 1990-Rodrigues, Maria Gabriela, 1965-Repositório da Universidade de LisboaRodrigues, José Alberto Correia Pereira202520242027-02-20T00:00:00Z2025-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.5/97781enginfo:eu-repo/semantics/embargoedAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T16:33:00Zoai:repositorio.ulisboa.pt:10400.5/97781Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T04:19:26.020867Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Role of microRNA-21-loaded extracellular vesicles in liver-muscle intercommunication during Metabolic Dysfunction–associated Steatotic Liver Disease
title Role of microRNA-21-loaded extracellular vesicles in liver-muscle intercommunication during Metabolic Dysfunction–associated Steatotic Liver Disease
spellingShingle Role of microRNA-21-loaded extracellular vesicles in liver-muscle intercommunication during Metabolic Dysfunction–associated Steatotic Liver Disease
Rodrigues, José Alberto Correia Pereira
Comunicação fígado para músculo
MASLD
miR-21
Sarcopenia
Vesículas extracelulares
Teses de mestrado - 2025
Departamento de Biologia Animal
title_short Role of microRNA-21-loaded extracellular vesicles in liver-muscle intercommunication during Metabolic Dysfunction–associated Steatotic Liver Disease
title_full Role of microRNA-21-loaded extracellular vesicles in liver-muscle intercommunication during Metabolic Dysfunction–associated Steatotic Liver Disease
title_fullStr Role of microRNA-21-loaded extracellular vesicles in liver-muscle intercommunication during Metabolic Dysfunction–associated Steatotic Liver Disease
title_full_unstemmed Role of microRNA-21-loaded extracellular vesicles in liver-muscle intercommunication during Metabolic Dysfunction–associated Steatotic Liver Disease
title_sort Role of microRNA-21-loaded extracellular vesicles in liver-muscle intercommunication during Metabolic Dysfunction–associated Steatotic Liver Disease
author Rodrigues, José Alberto Correia Pereira
author_facet Rodrigues, José Alberto Correia Pereira
author_role author
dc.contributor.none.fl_str_mv Simão, André Daniel Lopes, 1990-
Rodrigues, Maria Gabriela, 1965-
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Rodrigues, José Alberto Correia Pereira
dc.subject.por.fl_str_mv Comunicação fígado para músculo
MASLD
miR-21
Sarcopenia
Vesículas extracelulares
Teses de mestrado - 2025
Departamento de Biologia Animal
topic Comunicação fígado para músculo
MASLD
miR-21
Sarcopenia
Vesículas extracelulares
Teses de mestrado - 2025
Departamento de Biologia Animal
description Tese de mestrado, Biologia Evolutiva e do Desenvolvimento, 2025, Universidade de Lisboa, Faculdade de Ciências
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025-01-01T00:00:00Z
2027-02-20T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.5/97781
url http://hdl.handle.net/10400.5/97781
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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