PXD067091

PXD067091 is an original dataset announced via ProteomeXchange.

Title	Basement membrane turnover and circulating matrix biomarkers in kidney disease
Description	Chronic kidney disease (CKD) is characterised by kidney fibrosis and represents a major public health concern. Alport syndrome, a common monogenic cause of kidney failure caused by genetic variants in the type IV collagen genes COL4A3, COL4A4 or COL4A5, leads to abnormal basement membrane remodelling and kidney fibrosis. Understanding the dynamics and mechanisms of kidney matrix remodelling is crucial for directing emerging gene therapies and developing non-invasive biomarkers to detect and stage kidney fibrosis earlier, ultimately enabling risk stratification and timely intervention. To define the temporal and spatial dynamics of kidney matrix remodelling, we applied a multi-omics strategy in a Col4a5-/- mouse model of X-linked Alport syndrome, integrating stable isotope metabolic labelling, deep proteomic profiling, bulk RNA sequencing, super-resolution imaging, and bioinformatic prediction. Transcriptomic profiling identified enrichment of extracellular matrix degradation pathways and upregulation of matrix proteases. 13C-Lysine labelling coupled with mass spectrometry revealed altered abundance and accelerated turnover of basement membrane components in Alport kidneys. Super-resolution imaging confirmed spatial disorganisation of matrix proteins, supporting a loss of structural integrity. Using peptide location fingerprinting, we mapped damage modifications and predicted fragmentation in ~40 kidney matrix proteins, including collagens, laminins and nidogens. Targeted assays validated the presence of these predicted matrix fragments in serum from children with COL4A3–5 variants, demonstrating detectable alterations in circulating basement membrane peptides compared to healthy controls. These data define an uncoupling of matrix synthesis and degradation as a hallmark of Alport-associated kidney fibrosis. Our integrative approach establishes a framework for linking matrix proteolysis and basement membrane fragmentation with clinically accessible biomarkers of kidney matrix remodelling. The detection of circulating matrix fragments offers a promising non-invasive strategy to monitor basement membrane integrity and stage kidney fibrosis, with potential utility in both diagnosis and therapeutic response assessment in Alport syndrome and broader CKD contexts.
HostingRepository	PRIDE
AnnounceDate	2026-05-21
AnnouncementXML	Submission_2026-05-21_06:52:22.290.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anna Hoyle
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue; iodoacetic acid derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-07 13:24:07	ID requested
⏵ 1	2026-05-21 06:52:22	announced

10.1016/J.CELREP.2026.117356;

submitter keyword: ECM,kidney, Alports, turnover

Rachel Lennon
contact affiliation	Manchester Cell-Matrix Centre, Division of Cell-Matrix Biology and Regenerative Medicine, The University of Manchester
contact email	Rachel.Lennon@manchester.ac.uk
lab head
Anna Hoyle
contact affiliation	University of Oxford
contact email	anna.hoyle@kennedy.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD067091
     1. Label: PRIDE project
     2. Name: Basement membrane turnover and circulating matrix biomarkers in kidney disease