Dataset Information

Suppression of asthmatic phenotype and altered lipid metabolism in mice lacking zona pellucida binding protein 2

ABSTRACT: The human chromosomal region 17q12-q21 is associated with childhood asthma. It harbors 5 protein-coding genes, of which ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) and gasdermin B (GSDMB) are the top causal gene candidates. Emerging evidence suggests that the promoter region of another gene, the zona pellucida binding protein 2 (ZPBP2), located more than 50kb proximal to ORMDL3 may be critical for its transcriptional regulation influencing susceptibility to asthma. To test this hypothesis, we examined the lung phenotypes, liver transcriptomes and lipid metabolism of Zpbp2 knock-out (KO) mice. We found that in comparison to wild type (WT) mice, Zpbp2 KO mice sensitized with allergen ovalbumin (OVA) had reduced bronchial reactivity. The Zpbp2 KO mice also had altered lipid metabolism with a 3-fold decrease in the levels of docosahexaenoic acid (DHA), increased body weight and changes in the expression of the adipocytokine signaling pathway gene peroxisome proliferator activated receptor alpha (Pparα). The Zpbp2 deletion was also associated with increased DNA methylation at the Zpbp2 promoter/enhancer region, reminiscent of the methylation of the orthologous region in humans, and reduced expression of Ormdl3 in liver. The sum of our results implies that the Zpbp2 gene is involved in the regulation of airway hypersensitivity and lipid metabolism, either directly or through a cis-regulatory effect on Ormdl3.

ORGANISM(S): Mus musculus

PROVIDER: GSE98513 | GEO | 2018/04/05

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Ethnopharmacological relevance: Gubenfangxiao decoction (GBFXD) is a traditional Chinese medicine formula derived from Yupingfensan, an ancient formula widely used to treat respiratory diseases such as repeated respiratory infection, allergic rhinitis, bronchitis, and asthma. In recent years, GBFXD has been applied to efficaciously and safely treat asthma. However, the mechanism of GBFXD is still not fully elucidated. Aim of the study: A label-free proteomic method was to employed to explore the protective mechanism of GBFXD in respiratory syncytial virus (RSV)-ovalbumin (OVA)-induced chronic persistent asthmatic mice. Materials and methods: After RSV-OVA challenge, mice were orally administered GBFXD at a dose of 36 g/kg/d accompanied with OVA nasal spray once every 3 days for 28 days. The label-free proteomics-based liquid chromatography-tandem mass spectrometry method was used to explore the differentially abundant proteins (DAPs) in the serum from model mice compared with that in control mice (M:C), and in GBFXD-treated mice compared with that in model mice (G:M). We utilized OmicsBean (http://www.omicsbean.cn), a multi-omics data analysis platform, to perform bioinformatics analysis of DAPs. Enzyme-linked immunosorbent assay and Western Blotting were performed to measure the levels of related proteins and verify the results of proteomics analysis. Results: A total of 69 significant DAPs were identified including 39 in M:C, 46 in G:M, and 16 common differential proteins. Bioinformatics analysis revealed that the DAPs of M:C were mainly involved in inflammatory response and were related to lipid metabolism. However, the DAPs of G:M mostly participated in stress response, inflammatory response, and epithelial cell proliferation. Serum levels of Apoa-1, Apoc-1, Cfd, and Lrg1, EGFR and Lrg1 in the lungs were consistent with the results of proteomic analysis. Apoa-1 and Apoc-1 are closely related to cholesterol transport, lipid metabolism balance, and airway epithelial integrity; Cfd participates in immune response, affecting the occurrence and development of inflammation; EGFR and Lrg1 are involved in epithelial cell proliferation, influencing the process of airway remodeling. Conclusions: GBFXD may affect inflammatory and immune responses of asthma by regulating cholesterol transport and complement factor activation. Furthermore, it could repair damaged airway epithelium and avoid airway remodeling to prevent and treat asthma.

Dataset Information

Suppression of asthmatic phenotype and altered lipid metabolism in mice lacking zona pellucida binding protein 2

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets