PXD053691-1

PXD053691 is an original dataset announced via ProteomeXchange.

Title	Interleukin-8 mediated cellular crosstalk drives hypertrophic cardiomyopathy in LZTR1 2 deficiency
Description	LZTR1 deficiency causes Noonan syndrome (NS) and is associated with the manifestation of severe and early-onset hypertrophic cardiomyopathy (HCM). Although paracrine communication is thought to play a critical role in cardiac pathology, little is known about the underlying pathomechanism leading to the development of HCM and cardiac fibrosis in NS. In the present study, we used 2D and 3D iPSC models with LZTR1 deficiency to dissect the impact of non-cardiomyocytes in the development of NS-associated HCM and uncovered a cytokine mediated intercellular crosstalk, predominantly activated in the disease state, as a major driver of cardiac hypertrophy and cardiac fibrosis. We showed that cardiac fibroblast-specific secretion of interleukin-8 induces a fibrosis-related signature and potentiates cardiomyocyte 45 hypertrophy. Importantly, inhibition of IL-8 signaling reversed the pathological effects in 46 cardiac fibroblasts and cardiomyocytes and may serve as a novel therapeutic option for the 47 treatment of NS-associated HCM.
HostingRepository	PRIDE
AnnounceDate	2026-04-02
AnnouncementXML	Submission_2026-04-01_20:31:55.556.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christof Lenz
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-05 03:40:07	ID requested
⏵ 1	2026-04-01 20:31:56	announced

10.1161/CIRCULATIONAHA.125.074155;

submitter keyword: LZTR1, iPSCs,Noonan syndrome, CXCR1/2 51 inhibition, disease modeling, cardiac fibrosis, hypertrophic cardiomyopathy, interleukin-8, tissue engineering

Christof Lenz
contact affiliation	University Medical Center Goettingen, Department of Clinical Chemistry, Core Facility Proteomics
contact email	christof.lenz@uni-goettingen.de
lab head
Christof Lenz
contact affiliation	Max Planck Institute for Biophysical Chemistry
contact email	christof.lenz@mpibpc.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD053691

PRIDE project URI

• PRIDE
  1. PXD053691
     1. Label: PRIDE project
     2. Name: Interleukin-8 mediated cellular crosstalk drives hypertrophic cardiomyopathy in LZTR1 2 deficiency