Related Experiment Video
Updated: Jul 3, 2026
10:20
In vitro Measurements of Tracheal Constriction Using Mice
Published on: June 25, 2012
Esrrg Inhibition Protects against Fine Particulate Matter-induced Asthma Aggravation by Reducing Pde3b
Zhihua Zhang1,2, Tao Cai3, Xin Zhang4
1Department of Science and Education.
American Journal of Respiratory Cell and Molecular Biology
|March 28, 2025
Summary
Inhibiting Estrogen Related Receptor gamma (Esrrg) reduces airway inflammation and cell damage caused by PM2.5 exposure in asthma models. Esrrg targets phosphodiesterase 3B (Pde3b) to worsen PM2.5-induced asthma.
Area of Science:
- Environmental Health
- Molecular Biology
- Respiratory Medicine
Background:
- Particulate Matter 2.5 (PM2.5) exposure exacerbates asthma.
- Estrogen Related Receptor gamma (Esrrg) is a nuclear receptor involved in metabolic diseases.
- The role of Esrrg in PM2.5-induced asthma aggravation is unknown.
Purpose of the Study:
- To investigate the role of Esrrg in PM2.5-triggered asthma aggravation.
- To explore the therapeutic potential of Esrrg inhibition in a mouse model of PM2.5-aggravated asthma.
Main Methods:
- Established a mouse model of asthma aggravation by exposing ovalbumin (OVA)-sensitized mice to PM2.5.
- Utilized mRNA sequencing to identify differentially expressed genes, including Esrrg.
- Employed adeno-associated virus (AAV)-mediated shRNA (shEsrrg) and pharmacological inhibition (GSK5182) to suppress Esrrg in vivo and in vitro.
- Assessed airway inflammation, MTEC damage, and Pde3b expression.
- Confirmed Esrrg binding to the Pde3b promoter using dual luciferase reporter and ChIP-PCR assays.
Main Results:
- Esrrg was significantly upregulated in OVA-induced asthma and further increased by PM2.5 exposure.
- Esrrg inhibition (shEsrrg or GSK5182) ameliorated airway inflammation and MTEC injury in PM2.5-aggravated asthmatic mice.
- Esrrg inhibition reduced phosphodiesterase 3B (Pde3b) expression.
- Esrrg directly binds to the Pde3b promoter.
Conclusions:
- Esrrg inhibition alleviates airway inflammation in a PM2.5-aggravated asthma model.
- Esrrg inhibition prevents PM2.5-induced MTEC injury by targeting the Pde3b promoter.
- Esrrg is a potential therapeutic target for PM2.5-aggravated asthma.
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