Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease

[Background & Aims] Porto-sinusoidal vascular disease (PSVD) is a rare vascular liver disease of unknown etiology that causes portal hypertension. It usually affects young individuals and shortens live expectancy. The deregulated pathways involved in PSVD development are unknown and therefore we...

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Autores: Hernández-Gea, Virginia, Campreciós, Genís, Betancourt, Fabián, Pérez-Campuzano, Valeria, Seijo, Susana, Díaz, Alba, Gallego-Durán, Rocío, Olivas, Pol, Orts, Lara, Mahaz, Marta, Baiges, Anna, Turon, Fanny, Sidorova, Julia, Romero-Gómez, Manuel, Lozano, Juan José, García-Pagán, Juan Carlos
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/262938
Acceso en línea:http://hdl.handle.net/10261/262938
Access Level:acceso abierto
Palabra clave:Porto sinusoidal vascular disease
Non-cirrhotic portal hypertension
Portal hypertension
Vascular liver disease
Trasncriptomic analysis
System biology
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oai_identifier_str oai:digital.csic.es:10261/262938
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease
title Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease
spellingShingle Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease
Hernández-Gea, Virginia
Porto sinusoidal vascular disease
Non-cirrhotic portal hypertension
Portal hypertension
Vascular liver disease
Trasncriptomic analysis
System biology
title_short Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease
title_full Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease
title_fullStr Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease
title_full_unstemmed Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease
title_sort Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease
dc.creator.none.fl_str_mv Hernández-Gea, Virginia
Campreciós, Genís
Betancourt, Fabián
Pérez-Campuzano, Valeria
Seijo, Susana
Díaz, Alba
Gallego-Durán, Rocío
Olivas, Pol
Orts, Lara
Mahaz, Marta
Baiges, Anna
Turon, Fanny
Sidorova, Julia
Romero-Gómez, Manuel
Lozano, Juan José
García-Pagán, Juan Carlos
author Hernández-Gea, Virginia
author_facet Hernández-Gea, Virginia
Campreciós, Genís
Betancourt, Fabián
Pérez-Campuzano, Valeria
Seijo, Susana
Díaz, Alba
Gallego-Durán, Rocío
Olivas, Pol
Orts, Lara
Mahaz, Marta
Baiges, Anna
Turon, Fanny
Sidorova, Julia
Romero-Gómez, Manuel
Lozano, Juan José
García-Pagán, Juan Carlos
author_role author
author2 Campreciós, Genís
Betancourt, Fabián
Pérez-Campuzano, Valeria
Seijo, Susana
Díaz, Alba
Gallego-Durán, Rocío
Olivas, Pol
Orts, Lara
Mahaz, Marta
Baiges, Anna
Turon, Fanny
Sidorova, Julia
Romero-Gómez, Manuel
Lozano, Juan José
García-Pagán, Juan Carlos
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Educación y Ciencia (España)
Agència de Gestió d'Ajuts Universitaris i de Recerca
European Commission
Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España)
Hospital Clínic de Barcelona
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Porto sinusoidal vascular disease
Non-cirrhotic portal hypertension
Portal hypertension
Vascular liver disease
Trasncriptomic analysis
System biology
topic Porto sinusoidal vascular disease
Non-cirrhotic portal hypertension
Portal hypertension
Vascular liver disease
Trasncriptomic analysis
System biology
description [Background & Aims] Porto-sinusoidal vascular disease (PSVD) is a rare vascular liver disease of unknown etiology that causes portal hypertension. It usually affects young individuals and shortens live expectancy. The deregulated pathways involved in PSVD development are unknown and therefore we lack curative treatments. The purpose of this study was to integrate transcriptomic and clinical data by comprehensive network-based modeling in order to uncover altered biological processes in patients with PSVD.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
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/10261/262938
url http://hdl.handle.net/10261/262938
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO//SAF2016-75767-R
http://dx.doi.org/10.1016/j.jhep.2021.05.014
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869414985278423040
spelling Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular diseaseHernández-Gea, VirginiaCampreciós, GenísBetancourt, FabiánPérez-Campuzano, ValeriaSeijo, SusanaDíaz, AlbaGallego-Durán, RocíoOlivas, PolOrts, LaraMahaz, MartaBaiges, AnnaTuron, FannySidorova, JuliaRomero-Gómez, ManuelLozano, Juan JoséGarcía-Pagán, Juan CarlosPorto sinusoidal vascular diseaseNon-cirrhotic portal hypertensionPortal hypertensionVascular liver diseaseTrasncriptomic analysisSystem biology[Background & Aims] Porto-sinusoidal vascular disease (PSVD) is a rare vascular liver disease of unknown etiology that causes portal hypertension. It usually affects young individuals and shortens live expectancy. The deregulated pathways involved in PSVD development are unknown and therefore we lack curative treatments. The purpose of this study was to integrate transcriptomic and clinical data by comprehensive network-based modeling in order to uncover altered biological processes in patients with PSVD.[Methods] We obtained liver tissue samples from 20 consecutive patients with PSVD and 21 sex- and age-matched patients with cirrhosis and 13 histologically normal livers (HNL) (initial cohort) and performed transcriptomic analysis. Microarray data were analyzed using weighted gene correlation network analysis to identify clusters of highly correlated genes differently expressed in patients with PSVD. We next evaluated the molecular pathways enriched in patients with PSVD and the core-related genes from the most significantly enriched pathways in patients with PSVD. Our main findings were validated using RNA sequencing in a different cohort of PSVD, cirrhosis and HNL (n = 8 for each group).[Results] Patients with PSVD have a distinctive genetic profile enriched mainly in canonical pathways involving hemostasis and coagulation but also lipid metabolism and oxidative phosphorylation. Serpin family (SERPINC1), the apolipoproteins (APOA, APOB, APOC), ATP synthases (ATP5G1, ATP5B), fibrinogen genes (FGB, FGA) and alpha-2-macroglobulin were identified as highly connective genes that may have an important role in PSVD pathogenesis.[Conclusion] PSVD has a unique transcriptomic profile and we have identified deregulation of pathways involved in vascular homeostasis as the main pathogenic event of disease development. [Lay summary] Porto-sinusoidal vascular disease is a rare but life-shortening disease that affects mainly young people. Knowledge of the disrupted pathways involved in its development will help to identify novel therapeutic targets and new treatments. Using a systems biology approach, we identify that pathways regulating endothelial function and tone may act as drivers of porto-sinusoidal vascular disease.This study was supported by the Instituto de Salud Carlos III FIS PI17/00398, the Ministry of Education and Science, Spain (SAF-2016-75767-R); Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR-SGR2017-517) a grant from Generalitat de Catalunya, Fondo Europeo de Desarrollo Regional (FEDER) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), funded by Instituto de Salud Carlos III. Marta Magaz is a recipient of a Río Hortega grant from Instituto de Salud Carlos III. Pol Olivas has been funded by Contractes Clínic de Recerca ”Emili Letang-Josep Font’’ 2020, granted by Hospital Clínic de Barcelona.Peer reviewedElsevierInstituto de Salud Carlos IIIMinisterio de Educación y Ciencia (España)Agència de Gestió d'Ajuts Universitaris i de RecercaEuropean CommissionCentro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España)Hospital Clínic de BarcelonaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/262938reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//SAF2016-75767-Rhttp://dx.doi.org/10.1016/j.jhep.2021.05.014Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2629382026-05-22T06:33:51Z
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