PXD028173-1

PXD028173 is an original dataset announced via ProteomeXchange.

Title	A novel chronic ANCA associated vasculitis model suitable for targeting reveals matrisomal changes
Description	Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are severe inflammatory disorders that often lead to rapid and irreversible organ failure. Rapid progressive glomerulonephritis (RPGN) is a particularly frequent renal manifestation and often leads to extensive glomerular scarring and interstitial fibrosis, resulting in chronic kidney disease and end stage renal failure. Current management options of AAV and its sequelae are limited and common therapies have serious side effects that impair quality of life. A better understanding of the deleterious scarring process of AAV may help to identify novel mechanisms and potential targets for therapy. However, robust murine models of scarring RPGN are still lacking. Here, we present a novel murine model of severe RPGN that recapitulates both acute injury and the subsequent glomerular and interstitial scarring that is based on combined administration of antibodies against the glomerular basement membrane (GBM) and myeloperoxidase (MPO), and bacterial lipopolysaccharides (LPS). Renal injury presented with severe hematuria, glomerular necrosis and crescent formation at 12 days, and consequent glomerular scarring 29 days after initial treatment. We observed increased expression of matrisomal components such as collagens, fibronectin, tenascin-C, in accordance with human AAV as deduced from analysis of gene expression microarray data and tissue staining. Moreover, we observed tissue infiltration by neutrophils, macrophages, T cells and myofibroblasts upon injury. Inhibition of CXCR4 using AMD3100 led to histological and molecular changes in injury with reduced chemokine expression and lower immune cells activation. Using mass-spectrometric proteome analysis, we provide a comprehensive overview of molecular and cellular changes in our AAV model. Altogether, we demonstrate a novel RPGN model that enables the study of matrisomal changes both in disease and upon intervention, as exemplified via CXCR4 inhibition, which could prove to be a viable pharmacological tool and provide matrix as novel targeting opportunity.
HostingRepository	MassIVE
AnnounceDate	2022-01-19
AnnouncementXML	Submission_2022-01-19_00:26:28.844.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Miguel Cosenza-Contreras
SpeciesList	scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList	Carbamidomethyl
Instrument	Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-27 08:04:24	ID requested
⏵ 1	2022-01-19 00:26:29	announced

no publication

submitter keyword: vasculitis, mouse, kidney, dia, anca associated vasculitis

Oliver Schilling
contact affiliation	University of Freiburg
contact email	oliver.schilling@mol-med.uni-freiburg.de
lab head
Miguel Cosenza-Contreras
contact affiliation	UNIVERSIT�TSKLINIKUM FREIBURG
contact email	miguel.de.jesus.cosenza.contreras@uniklinik-freiburg.de
dataset submitter

MassIVE dataset URI

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