PXD012064

PXD012064 is an original dataset announced via ProteomeXchange.

Title	Analysis of the podocyte proteome of LPS 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_04:13:44.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

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-14 03:11:52	ID requested
⏵ 1	2020-07-29 04:13:46	announced

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]

submitter keyword: FSGS

podocyte, kidney, injury

Markus Rinschen
contact affiliation	University Hosptial 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

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PRIDE project URI

• PRIDE
  1. PXD012064
     1. Label: PRIDE project
     2. Name: Analysis of the podocyte proteome of LPS treated mice