Proteomic Analysis of Niemann-Pick Type C Hepatocytes Reveals Potential Therapeutic Targets for Liver Damage

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dc.article.number2159
dc.catalogadorgjm
dc.contributor.authorBalboa Castillo, Elisa Ivana
dc.contributor.authorMarín Marín, Tamara Alejandra
dc.contributor.authorOyarzún Isamitt, Juan Esteban
dc.contributor.authorContreras, Pablo S.
dc.contributor.authorHardt, Robert
dc.contributor.authorVan Den Bosch, Thea
dc.contributor.authorÁlvarez Rojas, Alejandra
dc.contributor.authorRebolledo Jaramillo, Boris
dc.contributor.authorKlein, Andres D.
dc.contributor.authorWinter, Dominic
dc.contributor.authorZanlungo Matsuhiro, Silvana
dc.date.accessioned2024-06-06T17:55:11Z
dc.date.available2024-06-06T17:55:11Z
dc.date.issued2021
dc.description.abstractNiemann-Pick type C disease (NPCD) is a lysosomal storage disorder caused by mutations in the NPC1 gene. The most affected tissues are the central nervous system and liver, and while significant efforts have been made to understand its neurological component, the pathophysiology of the liver damage remains unclear. In this study, hepatocytes derived from wild type and Npc1(-/-) mice were analyzed by mass spectrometry (MS)-based proteomics in conjunction with bioinformatic analysis. We identified 3832 proteins: 416 proteins had a p-value smaller than 0.05, of which 37% (n = 155) were considered differentially expressed proteins (DEPs), 149 of them were considered upregulated, and 6 were considered downregulated. We focused the analysis on pathways related to NPC pathogenic mechanisms, finding that the most significant changes in expression levels occur in proteins that function in the pathways of liver damage, lipid metabolism, and inflammation. Moreover, in the group of DEPs, 30% (n = 47) were identified as lysosomal proteins and 7% (n = 10) were identified as mitochondrial proteins. Importantly, we found that lysosomal DEPs, including CTSB/D/Z, LIPA, DPP7 and GLMP, and mitocondrial DEPs, AKR1B10, and VAT1 had been connected with liver fibrosis, damage, and steatosis in previous studies, validiting our dataset. Our study found potential therapeutic targets for the treatment of liver damage in NPCD.
dc.description.funderFONDEQUIP
dc.description.funderDeutsche Forschungsgemeinschaft
dc.description.funderComision Nacional de Investigacion Cientifica y Tecnologica-Chile: Fondecyt
dc.fechaingreso.objetodigital2024-06-06
dc.format.extent15 páginas
dc.fuente.origenORCID
dc.identifier.doi10.3390/cells10082159
dc.identifier.eissn2073-4409
dc.identifier.pubmedidMEDLINE:34440927
dc.identifier.urihttps://doi.org/10.3390/cells10082159
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/86554
dc.identifier.wosidWOS:000688953100001
dc.information.autorucEscuela de Medicina; Balboa Castillo, Elisa Ivana; S/I; 142402
dc.information.autorucEscuela de Medicina; Marín Marín, Tamara Alejandra; S/I; 249923
dc.information.autorucEscuela de Medicina; Oyarzún Isamitt, Juan Esteban; S/I; 171970
dc.information.autorucFacultad de Ciencias Biológicas; Álvarez Rojas, Alejandra; 0000-0002-8129-9280; 83681
dc.information.autorucEscuela de Medicina; Zanlungo Matsuhiro, Silvana; 0000-0001-8383-9829; 72650
dc.issue.numero8
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaCells
dc.rightsacceso abierto
dc.rights.licenseCC BY 4.0 ATTRIBUTION 4.0 INTERNATIONAL Deed
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectLiver damage
dc.subjectNiemann Pick type C disease
dc.subjectLysosomal storage disorder
dc.subjectProteomic analysis
dc.subjectMass spectrometry
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleProteomic Analysis of Niemann-Pick Type C Hepatocytes Reveals Potential Therapeutic Targets for Liver Damage
dc.typeartículo
dc.volumen10
sipa.codpersvinculados142402
sipa.codpersvinculados249923
sipa.codpersvinculados171970
sipa.codpersvinculados83681
sipa.codpersvinculados72650
sipa.trazabilidadORCID;2024-06-03
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