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PXD003872

PXD003872 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleResponse of podocytes to PAN - YAP-mediated mechanotransduction determines the podocyte's response to damage
DescriptionPodocytes are terminally differentiated cells at the kidney filtration barrier and exposed to considerable mechanical strain. Podocyte injury causes morphological changes as a result of cytoskeletal reorganizations and failure of the filtration barrier. The transcriptional co-activators YAP/TAZ are tightly controlled through hippo signaling and responsive to mechanical cues. Here, we show that YAP is upregulated upon podocyte injury to activate YAP-dependent target genes. This activation preceded the development of proteinuria. In contrast, similar perturbations of cells in culture did not reveal increased YAP activity but showed a downregulation of YAP/TAZ activity when cells were grown on stiff surface. However, culture of cells on soft matrix or inhibition of stress fiber formation allowed recapitulation of the damage-induced YAP upregulation indicating a mechanotransduction-dependent mechanism of YAP over-activity. Interestingly, increased expression of YAP targets was confirmed in renal biopsies from patients with glomerular disease. Consistently, pharmacological inhibition of YAP/TEAD activity ameliorated glomerular disease in vivo. These data suggest that perturbation of the mechanosensitive hippo signaling pathway may be a therapeutic principle in podocyte disease.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:03:47.102.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMarkus Rinschen
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02016-03-30 06:18:28ID requested
12017-04-19 05:09:05announced
22024-10-22 04:03:55announced2024-10-22: Updated project metadata.
Publication List
10.1126/scisignal.aaf8165;
Rinschen MM, Grahammer F, Hoppe AK, Kohli P, Hagmann H, Kretz O, Bertsch S, H, ö, hne M, G, ö, bel H, Bartram MP, Gandhirajan RK, Kr, ü, ger M, Brinkkoetter PT, Huber TB, Kann M, Wickstr, ö, m SA, Benzing T, Schermer B, YAP-mediated mechanotransduction determines the podocyte's response to damage. Sci Signal, 10(474):(2017) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: Human podocytes PAN
Contact List
Bernhard Schermer, Markus Rinschen
contact affiliationUniversity Hospital Cologne, CECAD
contact emailbernhard.schermer@uk-koeln.de
lab head
Markus Rinschen
contact affiliationKidney research center cologne
contact emailmarkus.rinschen@uk-koeln.de
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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