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PXD027821-1

PXD027821 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleInterval-based secretomics unravels the time-dependent acute phase response in hepatocyte model systems
DescriptionMass spectrometry based secretomics approaches preferentially utilize serum-free culture conditions to circumvent serum induced interference and enable sufficient analytical depth. However, this negatively affects a wide range of cellular functions and thus reduces the biological relevance. Moreover, the experimental time range is limited by the viability of cells under serum free culture conditions which results in potentially missing out a large fraction of transcriptionally regulated secretion events and feedback-loops. We present an “interval-based” secretomics workflow, that addresses the shortcomings of the serum-free secretomics approach, by probing protein secretion rates in short serum-free time windows. We applied this approach to unravel the time-resolved secretion in the hepatocyte model systems HepG2 and HepaRG after stimulation of the acute-phase response (APR), a cellular reaction to inflammatory stimuli that typically manifests over days. The integration of relative quantification using tandem mass tags (TMT) enabled precise monitoring of time dependent changes in the secretome over days. Cell line and cytokine specific changes were observed: IL1b directed the APR towards pathogen defense over three distinct chronological phases. In contrast, IL6 directed the APR towards regeneration. Cell surface shedding was pronounced upon IL1b stimulation and small molecule inhibition of ADAM and matrix metalloproteases identified induced as well as constitutive shedding events. Inhibition of ADAM proteases by TAPI-0 not only led to reduced shedding of the sorting receptor SORT1, but also an attenuated cytokine response suggesting a direct link between cell surface shedding and cytokine secretion rates.
HostingRepositoryPRIDE
AnnounceDate2022-05-04
AnnouncementXMLSubmission_2022-05-04_04:42:29.841.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSascha Knecht
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; methionine oxidation with neutral loss of 64 Da; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-08-09 06:34:51ID requested
12022-05-04 04:42:30announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Secretomics, interval-based secretomics, HepG2, HepaRG, IL1b, IL6, acute-phase response, liver, shedding
Contact List
Marcus Bantscheff
contact affiliationCellzome - a GSK company Meyerhofstrasse 1, 69117 HEIDELBERG
contact emailmarcus.x.bantscheff@gsk.com
lab head
Sascha Knecht
contact affiliationCellzome GmbH, a GSK company
contact emailsascha.knecht@me.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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