PXD012063 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Analysis of podocytes from doxorubicin treated mice |
Description | Podocyte injury is a major cause of chronic kidney disease, but the involved signaling pathways are largely unknown. Here, we used ultrasensitive proteomics to investigate the response of native podocytes from mice with Doxorubicin-induced injury. We observed perturbations of known propagating pathways of glomerular disease such as Jak-Stat signaling and cell adhesion but also in metabolism and proteins responding to mechanical stress. Using a phenotype-guided approach, we prioritized candidates by aligning proteinuria in individual mice with corresponding podocyte protein expression data. The protein Tropomodulin was decreased and correlated negatively with urinary albumin, and Villin and the mechanosensor protein Filamin-B were increased and correlated positively. We employed Drosophila nephrocytes for further functional analysis of prioritized proteins and studied filtration function and endocytosis. Loss of Villin and Tropomodulin led to an impaired function and reduced expression of endocytosis machineries as evidenced by nephrocyte garland proteomes. Loss of Cher, the orthologue of Filamin-B, led to increased endocytosis in nephrocytes, and Filamin-B abundance in single glomeruli correlated with the amount of deposited albumin in the same glomerulus in proteinuric rats. Filamin-B expression could also be increased by applying mechanical stress to podocytes in vitro, but Filamin-B was not increased in podocyte proteomes in LPS-induced injury despite similar regulation of pathways on the global proteome level. In conclusion, this study identified conserved mechanisms of podocyte stress response employing functional proteomics in purified native mouse podocytes and Drosophila nephrocytes. |
HostingRepository | PRIDE |
AnnounceDate | 2020-07-29 |
AnnouncementXML | Submission_2020-07-29_04:14:24.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Markus Rinschen |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-12-14 02:23:46 | ID requested | |
⏵ 1 | 2020-07-29 04:14:25 | announced | |
Publication List
Koehler S, Kuczkowski A, Kuehne L, J, ü, ngst C, Hoehne M, Grahammer F, Eddy S, Kretzler M, Beck BB, H, ö, hfeld J, Schermer B, Benzing T, Brinkkoetter PT, Rinschen MM, Proteome Analysis of Isolated Podocytes Reveals Stress Responses in Glomerular Sclerosis. J Am Soc Nephrol, 31(3):544-559(2020) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: FSGS, podocytes, chronic kidney disease |
Contact List
Markus Rinschen |
contact affiliation | University Hospital Cologne |
contact email | markus.rinschen@uk-koeln.de |
lab head | |
Markus Rinschen |
contact affiliation | Kidney research center cologne |
contact email | markus.rinschen@uk-koeln.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD012063
- Label: PRIDE project
- Name: Analysis of podocytes from doxorubicin treated mice