PXD058959

PXD058959 is an original dataset announced via ProteomeXchange.

Title	Human Epididymis Protein 4 Promotes Aberrant Epithelial-Fibroblast Crosstalk in Pulmonary Fibrosis
Description	Invasive lung myofibroblasts are the main cause of tissue remodeling in idiopathic pulmonary fibrosis (IPF). A key mechanism contributing to this important feature is aberrant crosstalk between the abnormal/injured lung epithelium and pulmonary fibroblasts. Here, we demonstrated that lungs from patients with IPF and from mice with bleomycin (BLM)-induced pulmonary fibrosis (PF) are characterized by the induction of human epididymis protein 4 (HE4) overexpression in epithelial cells. HE4 knockdown primarily in epithelial cells attenuated BLM-induced PF in mice, whereas the administration of recombinant mouse HE4 exacerbated fibrosis after BLM stimulation. Mechanistic analysis showed that HE4 and annexin II (ANXA2) specific binding enhanced the profibrotic phenotype in epithelial cells, and directly promoted lung fibroblast activation, leading to aberrant epithelial-fibroblast crosstalk and the persistent myofibroblast phenotype. The HE4 and ANXA2 binding site was located after the 30th amino acid at the N terminus of the HE4 molecule. Finally, intratracheal administration of HE4 shRNA lentivirus protected mice against BLM-induced PF. These data suggest that HE4 can serve as a novel therapeutic target in the treatment of IPF.
HostingRepository	iProX
AnnounceDate	2024-12-17
AnnouncementXML	Submission_2025-01-12_19:48:18.393.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhenshun Cheng
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-17 18:56:48	ID requested
⏵ 1	2025-01-12 19:48:18	announced

Dataset with its publication pending

submitter keyword: Idiopathic pulmonary fibrosis

Human epididymis protein 4

Annexin II

Zhenshun Cheng
contact affiliation	Zhongnan Hospital of Wuhan University
contact email	zhengweishuai@163.com
lab head
Zhenshun Cheng
contact affiliation	Zhongnan Hospital of Wuhan University
contact email	zhengweishuai@163.com
dataset submitter

iProX dataset URI