PXD030416

PXD030416 is an original dataset announced via ProteomeXchange.

Title	LC MS/MS of calcium-sensing receptor (CaSR) knockdown in cultured murine podocytes versus wildtype
Description	Calcimimetic agents allosterically increase the calcium (Ca2+) sensitivity of the calcium-sensing receptor (CaSR), which is expressed in the tubular system and to a lesser extent in podocytes. Activation of this receptor can reduce glomerular proteinuria and structural damage in proteinuric animal models. However, the precise role of the podocyte CaSR is still unclear. A CaSR knockdown in cultured murine podocytes and a podocyte-specific CaSR knockout in BALB/c mice were generated to study its role in proteinuria and kidney function. Podocyte CaSR knockdown abolished the calcimimetic R-568 mediated Ca2+-influx, disrupted the actin cytoskeleton, reduced cellular attachment and migration velocity. Adriamycin (ADR)-induced proteinuria enhanced glomerular CaSR expression in wild type mice. Albuminuria, podocyte foot process effacement, podocyte loss and glomerular sclerosis were significantly more pronounced in ADR-treated podocyte-specific CaSR knockout mice compared to wild type littermates. The co-treatment of WT mice with ADR and the calcimimetic cinacalcet reduced the proteinuria in WT, but not in podocyte specific CaSR knockout mice. In addition, four children with nephrotic syndrome, objecting glucocorticoid therapy, were treated with cinacalcet for 1 to 33 days. Proteinuria declined transiently by up to 96% and edema resolved. The activation of podocyte CaSR regulates key podocyte functions in vitro and reduces toxin induced proteinuria and glomerular damage in mice. Our findings suggest a potential novel role of CaSR signaling in control of glomerular disease. Proteomic samples: two backgrounds (CaSR Knockdown vs WT) two conditions (Treatment = 1µM R568 vs untreated control) two timepoints (24h and 48h) five replicates each 2 x 2 x 2 x 5 = 40 samples
HostingRepository	PRIDE
AnnounceDate	2022-05-31
AnnouncementXML	Submission_2022-05-31_08:46:40.641.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Moritz Lassé
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-15 04:32:36	ID requested
⏵ 1	2022-05-31 08:46:41	announced

Dataset with its publication pending

submitter keyword: murine, mouse, podocytes, calcium-sensing receptor, CaSR

Markus Matthias Rinschen
contact affiliation	III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
contact email	m.rinschen@uke.de
lab head
Moritz Lassé
contact affiliation	Zentrum für Innere Medizin, III. Medizinische Klinik und Poliklinik (Nephrologie/Rheumatologie/Endokrinologie), Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, Germany
contact email	moritz.lasse@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030416
     1. Label: PRIDE project
     2. Name: LC MS/MS of calcium-sensing receptor (CaSR) knockdown in cultured murine podocytes versus wildtype