METTL14/YTHDF1 mediates m6A modification of PTBP1 to regulate PDGF-BB-induced airway smooth muscle cell function

Canming Qiu1, Zhenzhu Liao1, Pingping Guo1

  • 1Department of Pulmonary and Critical Care Medicine, the Second Hospital of Longyan, Longyan City, Fujian, China.

PubMed
Abstract

Insights

Methyltransferase-like 14 (METTL14) and YTH domain-containing family Protein 1 (YTHDF1) mediate the m6A methylation of polypyrimidine tract-binding protein 1 (PTBP1). This epigenetic modification is crucial for airway smooth muscle cell function in asthma.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Respiratory Medicine

Background:

  • Airway smooth muscle cell (ASMC) proliferation and migration are key factors in asthma pathogenesis.
  • Platelet-derived growth factor-BB (PDGF-BB) is implicated in ASMC remodeling and asthma.
  • The roles of METTL14, YTHDF1, and PTBP1 in PDGF-BB-induced ASMC responses require elucidation.

Purpose of the Study:

  • To investigate the impact of METTL14, YTHDF1, and PTBP1 on PDGF-BB-stimulated ASMCs.
  • To explore the mechanism of m6A methylation in regulating ASMC behavior during asthma progression.

Main Methods:

  • ASMCs were treated with PDGF-BB to induce remodeling.
  • Cell proliferation, migration, invasion, inflammation, and oxidative stress were assessed.
  • mRNA and protein expression levels of key molecules were analyzed using RT-qPCR and western blotting.
  • RNA immunoprecipitation (RIP) and dual-luciferase assays were employed to study m6A modification and protein interactions.

Main Results:

  • PDGF-BB promoted ASMC proliferation, migration, invasion, inflammation, oxidative stress, and macrophage polarization.
  • Knockdown of PTBP1 reversed these PDGF-BB-induced effects.
  • METTL14 and YTHDF1 were found to facilitate the m6A methylation of PTBP1 mRNA.
  • Elevated PTBP1 expression counteracted the effects of METTL14, and METTL14 influenced NF-κB pathway proteins via PTBP1.

Conclusions:

  • METTL14 and YTHDF1 mediate the m6A methylation of PTBP1.
  • This m6A modification of PTBP1 is critical for regulating ASMC functional behavior induced by PDGF-BB in asthma.

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