PXD043630

PXD043630 is an original dataset announced via ProteomeXchange.

Title	ORMDL3-mediated bronchial epithelial pyroptosis leads to lung inflammatory in obese asthmatic mice
Description	Obese asthma is a chronic disease that poses a serious threat to children's health, resulting in more severe wheezing, earlier airway remodelling, and insensitivity to hormone therapy. Despite its clinical importance, knowledge on the underlying mechanisms of this disease remains limited. This study aimed to elucidate the pathogenesis of obese asthmatic utilizing a murine model. The present study randomly divided thirty female BALB/c mice into three groups: normal mice, asthmatic mice, and obese asthmatic mice. The mice were fed a with high-fat diet (HFD) to induce obesity. Asthmatic mice were subjected to ovalbumin (OVA) sensitization and challenge. Mice with obesity were then subjected to OVA sensitization and challenge to develop obese asthmatic. Airway remodelling was observed in obese asthmatic mice. Proteomic and bioinformatics analyses were conducted on lung tissues from obese asthmatic and normal mice. A total of 200 proteins were differentially expressed in obese asthmatic compared to normal mice; of these, 53% were upregulated and 47% were downregulated. Pathway analysis revealed that obese asthmatic primarily affected the lysosome, phagosome, and sphingolipid metabolism pathways. In addition, pyroptosis was observed in obese asthmatic, along with significant increases in pyroptosis-related factors. Orosomucoid like 3 (ORMDL3), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and Gasdermin-D (GSDMD) expression was examined, with particularly high expression levels observed in obese asthmatic mice. In vitro experiments demonstrated that overexpression of ORMDL3 in human bronchial epithelial (HBE) cells led to increased expression of NLRP3, GSDMD, and cathepsin D (CTSD). These findings suggest that ORMDL3 may regulate pyroptosis and subsequent airway remodelling in obese asthmatic, possibly via CTSD/NLRP3/GSDMD pathway.
HostingRepository	iProX
AnnounceDate	2023-07-07
AnnouncementXML	Submission_2023-10-26_00:25:52.031.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fan Liu
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-09 23:53:50	ID requested
1	2023-07-21 00:03:53	announced
⏵ 2	2023-10-26 00:25:52	announced	2023-10-26: Update publication information.

Liu F, Sun Y, Zhou Y, Gao Y, Song Q, Yang J, Xu C, Li G, mediated bronchial epithelial pyroptosis leads to lung inflammation in obese mice with asthma. Mol Med Rep, 28(4):(2023) [pubmed]

submitter keyword: ORMDL3, pyroptosis, lysosome, obese asthmatic, bronchial epithelial cell

Yan Sun
contact affiliation	Department of Pediatric Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University
contact email	sunyan6150@126.com
lab head
Fan Liu
contact affiliation	Department of Pediatric Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University
contact email	liufan5023@163.com
dataset submitter

iProX dataset URI