PXD063448

PXD063448 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomics of cellular mechanosensing reveals NFATC4 as a regulator of myofibroblast activity
Description	Feedback connections between tissue stiffness and cellular contractile forces can instruct cell identity and activity via a process referred to as mechanosensing. Specific phosphoproteome changes during mechanosensing are poorly characterized. In this work, we chart the global phosphoproteome dynamics of primary human lung fibroblasts sensing the stiffness of injury relevant fibronectin coated Poly(dimethylsiloxane) substrates. We discovered a key signaling threshold at a Young's modulus of eight kPa stiffness, above which cells activated a large number of pathways including RhoA, CK2A1, PKA, AMPK, AKT1, and Hippo-YAP1/TAZ mediated signaling. Time-resolved phosphoproteomics of cell spreading on stiff substrates revealed the temporal dynamics of these stiffness-sensitive signaling pathways. ECM substrate stiffness above eight kPA induced fibroblast contractility, cytoskeletal rearrangements, ECM secretion, and a fibroblast to myofibroblast transition. Our data indicate that phosphorylation of the transcriptional regulator NFATC4 at S213/S217 enhances myofibroblast activity, which is the key hallmark of fibrotic diseases. NFATC4 knock down cells display reduced stiffness induced collagen secretion, collagen gel contraction, and cell invasion, suggesting NFATC4 as a novel target for antifibrotic therapy.
HostingRepository	PRIDE
AnnounceDate	2026-06-02
AnnouncementXML	Submission_2026-06-02_12:45:40.104.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Safouane Kadri
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-29 07:24:36	ID requested
⏵ 1	2026-06-02 12:45:40	announced

Dataset with its publication pending

submitter keyword: Human lung fibroblast

Herbert Schiller
contact affiliation	Research Unit for Precision Regenerative Medicine, Helmholtz Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), Munich, Germany Institute of Experimental Pneumology, LMU University Hospital, Ludwig-Maximilians University, Munich, Germany
contact email	herbert.schiller@helmholtz-munich.de
lab head
Safouane Kadri
contact affiliation	Helmholtz-Muenchen
contact email	safouane.kadri@helmholtz-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063448
     1. Label: PRIDE project
     2. Name: Phosphoproteomics of cellular mechanosensing reveals NFATC4 as a regulator of myofibroblast activity