PXD066782-1

PXD066782 is an original dataset announced via ProteomeXchange.

Title	Essential role of Protein kinase R in the pathogenesis of pulmonary veno-occlusive disease
Description	Pulmonary veno-occlusive disease (PVOD) is a rare and severe form of pulmonary arterial hypertension, characterized by progressive obstruction of small pulmonary vessels and a lack of effective therapeutic options. Our previous research, utilizing a mitomycin C (MMC)-induced rat model, demonstrated that activation of the integrated stress response (ISR) via protein kinase R (PKR) is a critical driver of endothelial dysfunction and pulmonary vascular remodeling. However, it remains unclear whether PKR is the sole mediator of ISR activation and the pathogenesis of PVOD under the MMC treatment. In this study, we administered the same dose of MMC used in rats to control (Ctrl) and PKR knockout (KO) mice. Consistent with observations in rats, Ctrl mice exhibited ISR activation in the vascular endothelium and rapidly developed vascular remodeling in both arteries and veins following MMC treatment. In contrast, KO mice showed no evidence of ISR activation or vascular remodeling under same conditions. Proteomic analysis revealed that the PKR-ISR axis perturbs proteostasis in Ctrl mice but not in KO mice. These findings highlight the essential role of PKR-mediated ISR activation and the disruption of proteostasis in the pathogenesis of PVOD, placing PKR as a promising therapeutic target for this disease.
HostingRepository	PRIDE
AnnounceDate	2025-08-11
AnnouncementXML	Submission_2025-08-11_12:44:03.004.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Abhilash Barpanda
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-30 15:24:12	ID requested
⏵ 1	2025-08-11 12:44:03	announced

Dataset with its publication pending

submitter keyword: Protein Kinase R, Proteomics,PVOD

Arun Wiita
contact affiliation	Professor, Department of Laboratory Medicine, UCSF
contact email	Arun.Wiita@ucsf.edu
lab head
Abhilash Barpanda
contact affiliation	IIT Bombay
contact email	avilash94@iitb.ac.in
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066782
     1. Label: PRIDE project
     2. Name: Essential role of Protein kinase R in the pathogenesis of pulmonary veno-occlusive disease