PXD003864-1

PXD003864 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis glomeruli of PAN-treated rats
Description	Podocytes 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 hyper-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.
HostingRepository	PRIDE
AnnounceDate	2017-05-02
AnnouncementXML	Submission_2017-05-02_05:16:27.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Markus Rinschen
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-03-29 04:30:33	ID requested
⏵ 1	2017-05-02 05:16:28	announced

Dataset with its publication pending

curator keyword: Biological

submitter keyword: Rat, glomeruli, podocytes

bernhard schermer
contact affiliation	University Hospital Cologne
contact email	bernhard.schermer@uk-koeln.de
lab head
Markus Rinschen
contact affiliation	Kidney research center cologne
contact email	markus.rinschen@uk-koeln.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/05/PXD003864

PRIDE project URI

• PRIDE
  1. PXD003864
     1. Label: PRIDE project
     2. Name: Proteomic analysis glomeruli of PAN-treated rats