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PXD077129

PXD077129 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe secretory peptidase inhibitor R3HDML fine-tunes p38 MAPK phosphorylation and mesangial phenotypes during renal aging and disease
DescriptionSerine proteases and their inhibitors are the most abundant class of proteolytic enzymes, involved in numerous biological processes such as cellular crosstalk. However, their role in renal diseases remains controversial. In this study, we identify R3HDML as highly podocyte specific expressed and secreted putative serine peptidase inhibitor. CRISPR/Cas9-mediated generation of a novel floxed-R3hdml allele, demonstrated a regulatory function in renal aging and streptozotocin induced diabetic nephropathy. R3hdml knockout mice developed a hump-like thickening of the glomerular basement membrane, as well as mesangial expansion. Despite these morphological alterations, renal function was not impaired by loss of R3hdml in aging, diabetic nephropathy, and ischemia-reperfusion induced tubular injury and regeneration. Employing interactome analyses led to the identification of p38 MAPK signaling-related kinases, and N-terminal signaling peptide containing proteins, as R3HDML interactors. Consequently, activating Thr180/Tyr182 phosphorylation of p38 MAPK was suppressed by R3HDML in podocytes. In summary, we demonstrate a highly selective expression of the putative serine peptidase inhibitor R3HDML in podocytes and a protective regulatory role in kidney disease and aging.
HostingRepositoryMassIVE
AnnounceDate2026-05-20
AnnouncementXMLSubmission_2026-05-20_23:39:21.010.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterStefan Tholen
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-04-14 05:57:02ID requested
12026-05-20 23:39:21announced
Publication List
no publication
Keyword List
submitter keyword: R3h domain containing-like, R3HDML, Podocyte, MAPK, AKI, Diabetes, CKD, DatasetType:Proteomics
Contact List
Dr. Wibke Bechtel-Walz
contact affiliationUniversity Medical Center Freiburg
contact emailwibke.bechtel@uniklinik-freiburg.de
lab head
Stefan Tholen
contact affiliationUniklinik Freiburg
contact emailstefan.tholen@uniklinik-freiburg.de
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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