BMP9 Promotes an Epithelial Phenotype and a Hepatocyte-like Gene Expression Profile in Adult Hepatic Progenitor Cells

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dc.contributor.authorAddante, Annalisa
dc.contributor.authorGonzález-Corralejo, Carlos
dc.contributor.authorRoncero Romero, Cesáreo
dc.contributor.authorLazcanoiturburu, Nerea
dc.contributor.authorGarcía-Sáez, Juan
dc.contributor.authorHerrera González, Blanca María
dc.contributor.authorSánchez Muñoz, Aranzazu
dc.date.accessioned2024-06-26T11:33:28Z
dc.date.available2024-06-26T11:33:28Z
dc.date.issued2022-01-21
dc.description.abstractBone morphogenetic protein 9 (BMP9), a member of the TGF-β superfamily, has emerged as a new player in chronic liver diseases (CLDs). Its levels increase in the fibrotic liver where it promotes fibrogenesis. It also regulates hepatic progenitor cells (oval cells in rodents), a cell population that contributes to repopulate the liver and recover functionality upon severe damage, but it can also be pro-fibrogenic, depending upon the hepatic microenvironment. Here we analyze the effect of chronic exposure to BMP9 in oval cells. We show that cells chronically treated with BMP9 (B9T-OC) display a more epithelial and hepatocyte-like phenotype while acquiring proliferative and survival advantages. Since our previous studies had revealed a functional crosstalk between BMP9 and the HGF/c-Met signaling pathways in oval cells, we analyzed a possible role for HGF/c-Met in BMP9-induced long-term effects. Data evidence that active c-Met signaling is necessary to obtain maximum effects in terms of BMP9-triggered hepatocytic differentiation potential, further supporting functionally relevant cooperation between these pathways. In conclusion, our work reveals a novel action of BMP9 in liver cells and helps elucidate the mechanisms that serve to increase oval cell regenerative potential, which could be therapeutically modulated in CLD.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Ciencia, Innovación y Universidades (España)
dc.description.statuspub
dc.identifier.citationAddante, A.; González-Corralejo, C.; Roncero, C.; Lazcanoiturburu, N.; García-Sáez, J.; Herrera, B.; Sánchez, A. BMP9 Promotes an Epithelial Phenotype and a Hepatocyte-like Gene Expression Profile in Adult Hepatic Progenitor Cells. Cells 2022, 11, 365.
dc.identifier.doi10.3390/cells11030365
dc.identifier.issn2073-4409
dc.identifier.officialurlhttps://doi.org/10.3390/cells11030365
dc.identifier.urihttps://hdl.handle.net/20.500.14352/105272
dc.issue.number365
dc.journal.titleCells
dc.language.isoeng
dc.publisherMDPI
dc.relation.projectIDinfo:eu-repo/grantAgreement/MICIU//RTI2018-099098-B-100
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/PITN-GA-2012-316549
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII//PI10/00274
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu577.1
dc.subject.cdu577.2
dc.subject.keywordBMP9
dc.subject.keywordoval cells
dc.subject.keywordHGF
dc.subject.keywordc-MET
dc.subject.keyworddifferentiation
dc.subject.ucmBiología molecular (Farmacia)
dc.subject.ucmBioquímica (Farmacia)
dc.subject.unesco32 Ciencias Médicas
dc.titleBMP9 Promotes an Epithelial Phenotype and a Hepatocyte-like Gene Expression Profile in Adult Hepatic Progenitor Cells
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number11
dspace.entity.typePublication
relation.isAuthorOfPublication9a9954ff-78f6-4240-a192-b1e06ec2b49d
relation.isAuthorOfPublication5827f207-2122-4faf-b1f3-7576ac372d56
relation.isAuthorOfPublication5ad3e4ea-8ef8-42a2-8f7b-ff372dc8d837
relation.isAuthorOfPublication.latestForDiscovery9a9954ff-78f6-4240-a192-b1e06ec2b49d
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