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The hepatocyte proteome in organotypic rat liver models and the influence of the local microenvironment

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dc.contributor.authorVu, Lucas T.en
dc.contributor.authorOrbach, Sophia M.en
dc.contributor.authorRay, W. Keithen
dc.contributor.authorCassin, Margaret E.en
dc.contributor.authorRajagopalan, Padmavathyen
dc.contributor.authorHelm, Richard F.en
dc.contributor.departmentBiochemistryen
dc.contributor.departmentChemical Engineeringen
dc.contributor.departmentInstitute for Critical Technology and Applied Scienceen
dc.date.accessioned2018-01-08T14:22:03Zen
dc.date.available2018-01-08T14:22:03Zen
dc.date.issued2017-06-20en
dc.description.abstractBackground: Liver models that closely mimic the in vivo microenvironment are useful for understanding liver functions, capabilities, and intercellular communication processes. Three-dimensional (3D) liver models assembled using hepatocytes and liver sinusoidal endothelial cells (LSECs) separated by a polyelectrolyte multilayer (PEM) provide a functional system while also permitting isolation of individual cell types for proteomic analyses. Methods: To better understand the mechanisms and processes that underlie liver model function, hepatocytes were maintained as monolayers and 3D PEM-based formats in the presence or absence of primary LSECs. The resulting hepatocyte proteomes, the proteins in the PEM, and extracellular levels of urea, albumin and glucose after three days of culture were compared. Results: All systems were ketogenic and found to release glucose. The presence of the PEM led to increases in proteins associated with both mitochondrial and peroxisomal-based β-oxidation. The PEMs also limited production of structural and migratory proteins associated with dedifferentiation. The presence of LSECs increased levels of Phase I and Phase II biotransformation enzymes as well as several proteins associated with the endoplasmic reticulum and extracellular matrix remodeling. The proteomic analysis of the PEMs indicated that there was no significant change after three days of culture. These results are discussed in relation to liver model function. Conclusions: Heterotypic cell-cell and cell-ECM interactions exert different effects on hepatocyte functions and phenotypes.en
dc.description.versionPublished versionen
dc.format.extent15 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationProteome Science. 2017 Jun 20;15(1):12en
dc.identifier.doihttps://doi.org/10.1186/s12953-017-0120-6en
dc.identifier.issn1477-5956en
dc.identifier.orcidHelm, RF [0000-0001-5317-0925]en
dc.identifier.urihttp://hdl.handle.net/10919/81601en
dc.identifier.volume15en
dc.language.isoenen
dc.publisherBiomed Centralen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000405227100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectBiochemical Research Methodsen
dc.subjectBiochemistry & Molecular Biologyen
dc.subjectHepatocyteen
dc.subjectKetogenesisen
dc.subjectLiveren
dc.subjectPolyelectrolyte multilayeren
dc.subjectProteomicsen
dc.subjectCELL-CELL INTERACTIONSen
dc.subjectFARNESOID-X-RECEPTORen
dc.subjectIN-VITROen
dc.subjectGLUCOSE-METABOLISMen
dc.subjectNONPARENCHYMAL CELLSen
dc.subjectSYSTEMS BIOLOGYen
dc.subjectMONOLAYER-CULTURESen
dc.subjectCOLLAGEN SANDWICHen
dc.subjectDRUG-METABOLISMen
dc.subjectCANCER CELLSen
dc.titleThe hepatocyte proteome in organotypic rat liver models and the influence of the local microenvironmenten
dc.title.serialProteome Scienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Fralin Affiliated Facultyen

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