miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver disease
[Background] During chronic liver diseases, LSECs undergo a dedifferentiation process contributing to the development of hepatic microvascular dysfunction. Although microRNAs (miRNAs) have been associated with chronic liver disease, their role as modulators of liver endothelial phenotype is mostly u...
| Autores: | , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/391238 |
| Acceso en línea: | http://hdl.handle.net/10261/391238 https://api.elsevier.com/content/abstract/scopus_id/105005186329 |
| Access Level: | acceso abierto |
| Palabra clave: | LSEC Cirrhosis Endothelial-to-mesenchymal transition Hepatic microcirculation Quantum dots |
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miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver diseaseAbad Jordà, LaiaMartínez-Alcocer, AnaGuixé-Muntet, SergiHunt, Nicholas J.Westwood, Lara J.Lozano, Juan JoséGallego-Durán, RocíoCogger, Victoria C.Fernández-Iglesias, AnabelGracia-Sancho, JordiLSECCirrhosisEndothelial-to-mesenchymal transitionHepatic microcirculationQuantum dots[Background] During chronic liver diseases, LSECs undergo a dedifferentiation process contributing to the development of hepatic microvascular dysfunction. Although microRNAs (miRNAs) have been associated with chronic liver disease, their role as modulators of liver endothelial phenotype is mostly unknown. Therefore, the aim of this study was to analyze miRNAs as regulators of hepatic sinusoidal endothelial dysfunction in chronic liver disease to suggest novel and translatable therapeutic options for cirrhosis.[Methods] Global expression of miRNAs was determined in primary LSECs from healthy and cirrhotic patients (alcohol abuse) and rats (CCl4 inhalation). LSECs were transfected with the mimetic or inhibitor of dysregulated miRNAs or with quantum dot nano-complexes containing miR-27b-3p or negative control, and endothelial phenotype was analyzed by RNA sequencing, quantitative PCR, and western blot. Endothelial or mesenchymal phenotypes were analyzed in LSEC by RNA sequencing, followed by pathway analyses and gene deconvolution.[Results] In all, 30 and 69 dysregulated miRNAs were identified in human and rat cirrhosis, respectively, of which 6 miRNAs were commonly dysregulated. Specific exogenous downregulation of miR-27b-3p was associated with the upregulation of target genes, suggesting a correlation between loss of miR-27b-3p and LSEC dedifferentiation. Finally, the expression of miR-27b-3p was efficiently and physiologically re-established in cirrhotic LSECs using nano-miR-27b-3p, leading to modulation of 1055 genes compared with the negative control, ultimately leading to inhibition of the endothelial-to-mesenchymal transition process observed in cirrhosis.[Conclusions] Loss of miR-27b-3p expression contributes to LSECs dedifferentiation in cirrhosis. The use of nano-miR-27b-3p represents a new therapeutic option for hepatic diseases coursing with endothelial dysfunction.This project was supported by the Instituto de Salud Carlos III (FIS PI23/00945, AC24/00135, DTS22/00010, and DTS24/00035; co-funded by the European Union), the AGAUR-Generalitat de Catalunya (2021 SGR 01322 and 2021 PROD 00036), the Gilead International Scholarships in Liver Diseases and the CIBEREHD (EHD19PI04). CIBEREHD is funded by the Instituto de Salud Carlos III. The funders of this study had no role in study development, data collection, and analysis. Laia Abad-Jordà is supported by an iPFIS fellowship and AM-A by a PFIS fellowship, both from the Instituto de Salud Carlos III.Peer reviewedWolters KluwerInstituto de Salud Carlos IIIEuropean CommissionAgència de Gestió d'Ajuts Universitaris i de RecercaGilead Research ScholarsAbad Jordà, Laia [0000-0001-9689-8799]Fernández-Iglesias, Anabel [0000-0003-2364-6675]Gracia-Sancho, Jordi [0000-0001-7736-4089]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/391238https://api.elsevier.com/content/abstract/scopus_id/105005186329reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI http://doi.org/10.1097/HC9.0000000000000700http://doi.org/10.1097/HC9.0000000000000700Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3912382026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver disease |
| title |
miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver disease |
| spellingShingle |
miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver disease Abad Jordà, Laia LSEC Cirrhosis Endothelial-to-mesenchymal transition Hepatic microcirculation Quantum dots |
| title_short |
miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver disease |
| title_full |
miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver disease |
| title_fullStr |
miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver disease |
| title_full_unstemmed |
miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver disease |
| title_sort |
miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver disease |
| dc.creator.none.fl_str_mv |
Abad Jordà, Laia Martínez-Alcocer, Ana Guixé-Muntet, Sergi Hunt, Nicholas J. Westwood, Lara J. Lozano, Juan José Gallego-Durán, Rocío Cogger, Victoria C. Fernández-Iglesias, Anabel Gracia-Sancho, Jordi |
| author |
Abad Jordà, Laia |
| author_facet |
Abad Jordà, Laia Martínez-Alcocer, Ana Guixé-Muntet, Sergi Hunt, Nicholas J. Westwood, Lara J. Lozano, Juan José Gallego-Durán, Rocío Cogger, Victoria C. Fernández-Iglesias, Anabel Gracia-Sancho, Jordi |
| author_role |
author |
| author2 |
Martínez-Alcocer, Ana Guixé-Muntet, Sergi Hunt, Nicholas J. Westwood, Lara J. Lozano, Juan José Gallego-Durán, Rocío Cogger, Victoria C. Fernández-Iglesias, Anabel Gracia-Sancho, Jordi |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Instituto de Salud Carlos III European Commission Agència de Gestió d'Ajuts Universitaris i de Recerca Gilead Research Scholars Abad Jordà, Laia [0000-0001-9689-8799] Fernández-Iglesias, Anabel [0000-0003-2364-6675] Gracia-Sancho, Jordi [0000-0001-7736-4089] Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
LSEC Cirrhosis Endothelial-to-mesenchymal transition Hepatic microcirculation Quantum dots |
| topic |
LSEC Cirrhosis Endothelial-to-mesenchymal transition Hepatic microcirculation Quantum dots |
| description |
[Background] During chronic liver diseases, LSECs undergo a dedifferentiation process contributing to the development of hepatic microvascular dysfunction. Although microRNAs (miRNAs) have been associated with chronic liver disease, their role as modulators of liver endothelial phenotype is mostly unknown. Therefore, the aim of this study was to analyze miRNAs as regulators of hepatic sinusoidal endothelial dysfunction in chronic liver disease to suggest novel and translatable therapeutic options for cirrhosis. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/391238 https://api.elsevier.com/content/abstract/scopus_id/105005186329 |
| url |
http://hdl.handle.net/10261/391238 https://api.elsevier.com/content/abstract/scopus_id/105005186329 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI http://doi.org/10.1097/HC9.0000000000000700 http://doi.org/10.1097/HC9.0000000000000700 Sí |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Wolters Kluwer |
| publisher.none.fl_str_mv |
Wolters Kluwer |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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15.812429 |