PXD072214-1

PXD072214 is an original dataset announced via ProteomeXchange.

Title	Integrin alpha1 beta1 promotes interstitial fibrosis and cyst growth in a mouse model of polycystic kidney disease
Description	Background: Cystogenesis and interstitial fibrosis are contributing factors to kidney failure in individuals with autosomal dominant polycystic kidney disease (ADPKD). The molecular and cellular mechanisms involved in cyst growth and fibrosis are complex and new therapies are urgently needed to improve clinical outcomes. Methods: We used mass spectrometry-based proteomics to identify molecular changes in the Pkd1nl/nl mouse model of ADPKD and selected integrin-α1 as a candidate of interest to follow up in functional studies. Mice lacking integrin-α1 (Itga1-/-) were crossed to Pkd1nl/nl mice and effects on kidney function and kidney histology were measured. We investigated the effects of integrin-α1 depletion on fibrosis markers using qRT-PCR, western blot and immunofluorescence. Results: Proteomic analysis of the Pkd1nl/nl mouse showed increased abundance of integrin-α1. In human ADPKD tissue and two single cell RNA kidney disease datasets, ITGA1 was also upregulated. To investigate the functional role of this integrin subunit in ADPKD, we generated a Pkd1nl/nlItga1-/- mouse. We observed a significant reduction in kidney volume and kidney dysfunction in Pkd1nl/nl mice lacking integrin-α1. Kidneys from Pkd1nl/nlItga1-/- mice had smaller cysts, reduced interstitial expansion and less tubular atrophy. The myofibroblast marker alpha-smooth muscle actin remained switched on in Pdgfrb+ stromal cells of Pkd1nl/nlItga1-/- kidneys, suggesting integrin-α1 is not needed for activation of fibroblasts. Analysis of cell proliferation markers suggested that integrin-α1 promoted fibroblast expansion in response to cystic injury. Conclusions: These results highlight a previously unrecognised role for integrin-α1 in cyst growth and fibrosis in polycystic kidney disease.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-07_04:31:44.414.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD072214
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Richard Naylor
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-19 13:33:33	ID requested
⏵ 1	2026-09-07 04:31:45	announced

Grenier C, Lin IH, Peters DJM, Pozzi A, Lennon R, Naylor RW, 1 Promotes Interstitial Fibrosis and Cyst Growth in a Mouse Model of Polycystic Kidney Disease. J Am Soc Nephrol, 37(5):959-973(2026) [pubmed]

10.6019/PXD072214;

10.1681/asn.0000000941;

submitter keyword: ECM, cyst,Kidney, integrin

Richard Naylor
contact affiliation	University of Manchester, Manchester, United Kingdom
contact email	richard.naylor-2@manchester.ac.uk
lab head
Richard Naylor
contact affiliation	University of Manchester
contact email	richard.naylor-2@manchester.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD072214
     1. Label: PRIDE project
     2. Name: Integrin alpha1 beta1 promotes interstitial fibrosis and cyst growth in a mouse model of polycystic kidney disease