Rilpivirine Activates STAT1 in Non-Parenchymal Cells to Regulate Liver Injury in People Living with HIV and MASLD

Liver fibrosis is a key determinant of the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Its increasing prevalence and a lack of effective treatments make it a major health problem worldwide, particularly in people living with HIV, among whom the prevalence of adva...

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Autores: Moragrega, Ángela B., Busca, Carmen, Apostolova, Nadezda, Olveira, Antonio, Martín Carbonero, Luz, Valencia, Eulalia, Moreno, Victoria, Bernardino, José I., Abadía, Marta, González García, Juan, Esplugues, Juan V., Montes, María L., Blas García, Ana
Tipo de recurso: informe técnico
Fecha de publicación:2024
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/753760
Acceso en línea:https://hdl.handle.net/10486/753760
https://dx.doi.org/10.3390/biomedicines12071454
Access Level:acceso abierto
Palabra clave:fibrosis
MASH
hepatic stellate cells
antiretroviral therapy
Medicina
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spelling Rilpivirine Activates STAT1 in Non-Parenchymal Cells to Regulate Liver Injury in People Living with HIV and MASLDMoragrega, Ángela B.Busca, CarmenApostolova, NadezdaOlveira, AntonioMartín Carbonero, LuzValencia, EulaliaMoreno, VictoriaBernardino, José I.Abadía, MartaGonzález García, JuanEsplugues, Juan V.Montes, María L.Blas García, AnafibrosisMASHhepatic stellate cellsantiretroviral therapyMedicinaLiver fibrosis is a key determinant of the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Its increasing prevalence and a lack of effective treatments make it a major health problem worldwide, particularly in people living with HIV, among whom the prevalence of advanced fibrosis is higher. We have published preclinical data showing that Rilpivirine (RPV), a widely used anti-HIV drug, selectively triggers hepatic stellate cell (HSC) inactivation and apoptosis through signal transducer and activator of transcription (STAT)1-mediated pathways, effects that clearly attenuate liver fibrosis and promote regeneration. We performed a retrospective, cross-sectional study of RPV-induced effects on steatosis, inflammation, and fibrosis in liver biopsies from well-controlled HIV-infected subjects diagnosed with MASLD. Patients on RPV exhibited similar levels of HIV-related parameters to those not receiving this drug, while showing a tendency toward improved liver function and lipid profile, as well as an enhanced activation of STAT1 in hepatic non-parenchymal cells in those with identified liver injury. This protective effect, promoting STAT1-dependent HSC inactivation, was observed at different stages of MASLD. Our results suggest that RPV-based therapy is especially indicated in HIV-infected patients with MASLD-derived liver injury and highlight the potential of RPV as a new therapeutic strategy for liver diseasesThis research was funded by grants CIBER CB06/04/0071 (Instituto de Salud Carlos III), PID2021-127945OB-I00 (Ministerio de Ciencia e Innovación MCIN/AEI/10.13039/501100011033, co-funded by the European Regional Development Fund of the European Union—A way to make Europe), AICO2021/017 and CIPROM/2021/044 (Conselleria d’Educació, Formació i Empleo, Generalitat Valenciana), UGP-21-236 (FISABIO) and PI17/01218 (Plan Nacional R + D + I, co-funded by Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación). Á.B.M. is the recipient of a Predoctoral Trainee Research Grant (FPU16/05896, Ministerio de Educación, Cultura y Deporte)MDPIFacultad de MedicinaDepartamento de MedicinaGobierno de EspañaInstituto de Salud Carlos III20242024-06-29reporthttp://purl.org/coar/resource_type/c_93fcVoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/reportapplication/pdfhttps://hdl.handle.net/10486/753760https://dx.doi.org/10.3390/biomedicines1207145439062027reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7537602026-06-23T12:46:27Z
dc.title.none.fl_str_mv Rilpivirine Activates STAT1 in Non-Parenchymal Cells to Regulate Liver Injury in People Living with HIV and MASLD
title Rilpivirine Activates STAT1 in Non-Parenchymal Cells to Regulate Liver Injury in People Living with HIV and MASLD
spellingShingle Rilpivirine Activates STAT1 in Non-Parenchymal Cells to Regulate Liver Injury in People Living with HIV and MASLD
Moragrega, Ángela B.
fibrosis
MASH
hepatic stellate cells
antiretroviral therapy
Medicina
title_short Rilpivirine Activates STAT1 in Non-Parenchymal Cells to Regulate Liver Injury in People Living with HIV and MASLD
title_full Rilpivirine Activates STAT1 in Non-Parenchymal Cells to Regulate Liver Injury in People Living with HIV and MASLD
title_fullStr Rilpivirine Activates STAT1 in Non-Parenchymal Cells to Regulate Liver Injury in People Living with HIV and MASLD
title_full_unstemmed Rilpivirine Activates STAT1 in Non-Parenchymal Cells to Regulate Liver Injury in People Living with HIV and MASLD
title_sort Rilpivirine Activates STAT1 in Non-Parenchymal Cells to Regulate Liver Injury in People Living with HIV and MASLD
dc.creator.none.fl_str_mv Moragrega, Ángela B.
Busca, Carmen
Apostolova, Nadezda
Olveira, Antonio
Martín Carbonero, Luz
Valencia, Eulalia
Moreno, Victoria
Bernardino, José I.
Abadía, Marta
González García, Juan
Esplugues, Juan V.
Montes, María L.
Blas García, Ana
author Moragrega, Ángela B.
author_facet Moragrega, Ángela B.
Busca, Carmen
Apostolova, Nadezda
Olveira, Antonio
Martín Carbonero, Luz
Valencia, Eulalia
Moreno, Victoria
Bernardino, José I.
Abadía, Marta
González García, Juan
Esplugues, Juan V.
Montes, María L.
Blas García, Ana
author_role author
author2 Busca, Carmen
Apostolova, Nadezda
Olveira, Antonio
Martín Carbonero, Luz
Valencia, Eulalia
Moreno, Victoria
Bernardino, José I.
Abadía, Marta
González García, Juan
Esplugues, Juan V.
Montes, María L.
Blas García, Ana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Facultad de Medicina
Departamento de Medicina
Gobierno de España
Instituto de Salud Carlos III
dc.subject.none.fl_str_mv fibrosis
MASH
hepatic stellate cells
antiretroviral therapy
Medicina
topic fibrosis
MASH
hepatic stellate cells
antiretroviral therapy
Medicina
description Liver fibrosis is a key determinant of the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Its increasing prevalence and a lack of effective treatments make it a major health problem worldwide, particularly in people living with HIV, among whom the prevalence of advanced fibrosis is higher. We have published preclinical data showing that Rilpivirine (RPV), a widely used anti-HIV drug, selectively triggers hepatic stellate cell (HSC) inactivation and apoptosis through signal transducer and activator of transcription (STAT)1-mediated pathways, effects that clearly attenuate liver fibrosis and promote regeneration. We performed a retrospective, cross-sectional study of RPV-induced effects on steatosis, inflammation, and fibrosis in liver biopsies from well-controlled HIV-infected subjects diagnosed with MASLD. Patients on RPV exhibited similar levels of HIV-related parameters to those not receiving this drug, while showing a tendency toward improved liver function and lipid profile, as well as an enhanced activation of STAT1 in hepatic non-parenchymal cells in those with identified liver injury. This protective effect, promoting STAT1-dependent HSC inactivation, was observed at different stages of MASLD. Our results suggest that RPV-based therapy is especially indicated in HIV-infected patients with MASLD-derived liver injury and highlight the potential of RPV as a new therapeutic strategy for liver diseases
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-06-29
dc.type.none.fl_str_mv report
http://purl.org/coar/resource_type/c_93fc
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/report
format report
dc.identifier.none.fl_str_mv https://hdl.handle.net/10486/753760
https://dx.doi.org/10.3390/biomedicines12071454
39062027
url https://hdl.handle.net/10486/753760
https://dx.doi.org/10.3390/biomedicines12071454
identifier_str_mv 39062027
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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