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  1. Home
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Esrrg Inhibition Protects Against PM2.5-induced Asthma Aggravation by Reducing Pde3b

Zhihua Zhang1,2, Tao Cai3, Xin Zhang4

  • 1Hebei Chest Hospital, Department of Science and Education, Shijiazhuang, Hebei, China.

American Journal of Respiratory Cell and Molecular Biology
|March 28, 2025

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View abstract on PubMed

Summary

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  • Engineering
  • Environmental Engineering
  • Air Pollution Modelling And Control
  • Esrrg Inhibition Protects Against Pm2.5-induced Asthma Aggravation By Reducing Pde3b
  • This summary is machine-generated.

    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.
    Keywords:
    EsrrgPM2.5Pde3basthmatranscriptional regulation

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