Novel carbon-based nanoscale therapeutics for the modulation of macrophages in liver inflammation, fibrosis, and regeneration

[eng] INTRODUCTION: Chronic liver disease (CHD) is the consequence of prolonged liver damage and is characterized by a process of inflammation and fibrosis in the liver, which causes about 2 million deaths per year. It can take several years for CHD to progress from early fibrosis to cirrhosis, ulti...

Descripción completa

Detalles Bibliográficos
Autor: Moreno Lanceta, Alazne
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/216988
Acceso en línea:https://hdl.handle.net/2445/216988
http://hdl.handle.net/10803/692698
Access Level:acceso abierto
Palabra clave:Macròfags
Inflamació
Regeneració (Biologia)
Malalties del fetge
Macrophages
Inflammation
Regeneration (Biology)
Liver diseases
id ES_26b94fccb7a11f127d71d10f2eb9908f
oai_identifier_str oai:diposit.ub.edu:2445/216988
network_acronym_str ES
network_name_str España
repository_id_str
spelling Novel carbon-based nanoscale therapeutics for the modulation of macrophages in liver inflammation, fibrosis, and regenerationMoreno Lanceta, AlazneMacròfagsInflamacióRegeneració (Biologia)Malalties del fetgeMacrophagesInflammationRegeneration (Biology)Liver diseases[eng] INTRODUCTION: Chronic liver disease (CHD) is the consequence of prolonged liver damage and is characterized by a process of inflammation and fibrosis in the liver, which causes about 2 million deaths per year. It can take several years for CHD to progress from early fibrosis to cirrhosis, ultimately leading to liver failure and death. There are currently no curative therapies for cirrhosis beyond liver transplantation and, therefore, the development of new therapeutic strategies is necessary. Hepatic macrophages play essential roles in all stages of CHD, both in the initiation and progression of the inflammatory response and in the development of fibrosis. The microenvironment of chronic liver inflammation perpetuates the pro-inflammatory and profibrogenic activity of hepatic macrophages. However, macrophages are also essential in the processes that regulate the resolution of fibrosis, both by promoting an anti-inflammatory and regenerative response, and by secreting enzymes that remodel the extracellular matrix. Peroxisome proliferator-activated receptor gamma (PPARγ) and E3 ubiquitin ligase RNF41 have been associated with anti-inflammatory polarization of macrophages. HYPOTHESIS: Selective activation of the anti-inflammatory pathways PPARγ and RNF41 in hepatic macrophages by macrophage-selective carbon nanoparticles may induce a pro-resolutive phenotype in these immune cells that promotes a reduction in inflammation and fibrosis, and stimulates liver regeneration in CHD.[spa] INTRODUCCIÓN: La enfermedad hepática crónica (EHC) es la consecuencia de un daño hepático prolongado y se caracteriza por un proceso de inflamación y fibrosis en el hígado, que causa alrededor de 2 millones de muertes al año. La EHC puede tardar varios años en progresar desde fibrosis temprana hasta cirrosis, y en última instancia, producir insuficiencia hepática y muerte. Actualmente no existen terapias curativas para la cirrosis más allá del trasplante hepático y, por tanto, es necesario el desarrollo de nuevas estrategias terapéuticas. Los macrófagos hepáticos desempeñan funciones esenciales en todas las etapas de la EHC, tanto en el inicio y progresión de la respuesta inflamatoria como en el desarrollo de fibrosis. El microentorno de inflamación hepática crónica perpetúa la actividad proinflamatoria y profibrogénica de los macrófagos hepáticos. Sin embargo, los macrófagos también son esenciales en los procesos que regulan la resolución de la fibrosis, tanto promoviendo una respuesta antiinflamatoria y regenerativa, como mediante la secreción de enzimas que remodelen la matriz extracelular. El receptor gamma activado por el proliferador de peroxisomas (PPARγ) y la E3 ubiquitina ligasa RNF41 se han asociado a la polarización antiinflamatoria de los macrófagos. HIPÓTESIS: La activación selectiva de las vías antiinflamatorias PPARγ y RNF41 en macrófagos hepáticos mediante nanopartículas de carbono macrófago-selectivas puede inducir un fenotipo pro-resolutivo en estas células inmunitarias que promueva una reducción de la inflamación y la fibrosis, y estimule la regeneración del hígado en la EHC.Universitat de BarcelonaMelgar Lesmes, PedroUniversitat de Barcelona. Facultat de Medicina i Ciències de la Salut2024info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/216988http://hdl.handle.net/10803/692698Tesis Doctorals - Facultat - Medicina i Ciències de la Salutreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaEspañolcc by-nc-nd (c) Moreno Lanceta, Alazne, 2024http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2169882026-05-27T06:46:51Z
dc.title.none.fl_str_mv Novel carbon-based nanoscale therapeutics for the modulation of macrophages in liver inflammation, fibrosis, and regeneration
title Novel carbon-based nanoscale therapeutics for the modulation of macrophages in liver inflammation, fibrosis, and regeneration
spellingShingle Novel carbon-based nanoscale therapeutics for the modulation of macrophages in liver inflammation, fibrosis, and regeneration
Moreno Lanceta, Alazne
Macròfags
Inflamació
Regeneració (Biologia)
Malalties del fetge
Macrophages
Inflammation
Regeneration (Biology)
Liver diseases
title_short Novel carbon-based nanoscale therapeutics for the modulation of macrophages in liver inflammation, fibrosis, and regeneration
title_full Novel carbon-based nanoscale therapeutics for the modulation of macrophages in liver inflammation, fibrosis, and regeneration
title_fullStr Novel carbon-based nanoscale therapeutics for the modulation of macrophages in liver inflammation, fibrosis, and regeneration
title_full_unstemmed Novel carbon-based nanoscale therapeutics for the modulation of macrophages in liver inflammation, fibrosis, and regeneration
title_sort Novel carbon-based nanoscale therapeutics for the modulation of macrophages in liver inflammation, fibrosis, and regeneration
dc.creator.none.fl_str_mv Moreno Lanceta, Alazne
author Moreno Lanceta, Alazne
author_facet Moreno Lanceta, Alazne
author_role author
dc.contributor.none.fl_str_mv Melgar Lesmes, Pedro
Universitat de Barcelona. Facultat de Medicina i Ciències de la Salut
dc.subject.none.fl_str_mv Macròfags
Inflamació
Regeneració (Biologia)
Malalties del fetge
Macrophages
Inflammation
Regeneration (Biology)
Liver diseases
topic Macròfags
Inflamació
Regeneració (Biologia)
Malalties del fetge
Macrophages
Inflammation
Regeneration (Biology)
Liver diseases
description [eng] INTRODUCTION: Chronic liver disease (CHD) is the consequence of prolonged liver damage and is characterized by a process of inflammation and fibrosis in the liver, which causes about 2 million deaths per year. It can take several years for CHD to progress from early fibrosis to cirrhosis, ultimately leading to liver failure and death. There are currently no curative therapies for cirrhosis beyond liver transplantation and, therefore, the development of new therapeutic strategies is necessary. Hepatic macrophages play essential roles in all stages of CHD, both in the initiation and progression of the inflammatory response and in the development of fibrosis. The microenvironment of chronic liver inflammation perpetuates the pro-inflammatory and profibrogenic activity of hepatic macrophages. However, macrophages are also essential in the processes that regulate the resolution of fibrosis, both by promoting an anti-inflammatory and regenerative response, and by secreting enzymes that remodel the extracellular matrix. Peroxisome proliferator-activated receptor gamma (PPARγ) and E3 ubiquitin ligase RNF41 have been associated with anti-inflammatory polarization of macrophages. HYPOTHESIS: Selective activation of the anti-inflammatory pathways PPARγ and RNF41 in hepatic macrophages by macrophage-selective carbon nanoparticles may induce a pro-resolutive phenotype in these immune cells that promotes a reduction in inflammation and fibrosis, and stimulates liver regeneration in CHD.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/216988
http://hdl.handle.net/10803/692698
url https://hdl.handle.net/2445/216988
http://hdl.handle.net/10803/692698
dc.language.none.fl_str_mv Español
language_invalid_str_mv Español
dc.rights.none.fl_str_mv cc by-nc-nd (c) Moreno Lanceta, Alazne, 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Moreno Lanceta, Alazne, 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Facultat - Medicina i Ciències de la Salut
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404843253170176
score 15.198674

Similares en LA Referencia