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Updated: Sep 20, 2025

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METTL3 regulates ASMCs proliferation and M2 macrophage polarization via mediating the m6A methylation of TIMMDC1 in

Shihao Zhang1, Xiurong Wen1, Lin Liu2

  • 1Department of Respiratory and Critical Care Medicine, Ganzhou People's Hospital, Ganzhou, China.

Immunobiology
|May 23, 2025
PubMed
Abstract

Insights

Methyltransferase-like 3 (METTL3) suppresses asthma progression by inhibiting translocase of inner mitochondrial membrane domain-containing protein 1 (TIMMDC1) expression. This finding offers new insights into potential asthma treatments.

Area of Science:

  • Molecular Biology
  • Immunology
  • Respiratory Medicine

Background:

  • Asthma affects individuals of all ages, with its underlying mechanisms requiring further elucidation.
  • The roles of methyltransferase-like 3 (METTL3) and translocase of inner mitochondrial membrane domain-containing protein 1 (TIMMDC1) in asthma pathogenesis remain largely unknown.

Purpose of the Study:

  • To investigate the functional roles of METTL3 and TIMMDC1 in asthma.
  • To explore the regulatory relationship between METTL3 and TIMMDC1 in airway smooth muscle cells.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and Western blot for gene and protein expression analysis.
  • EdU and Transwell assays for cell proliferation and invasion.
  • Flow cytometry and qRT-PCR for apoptosis and M2 macrophage polarization.
  • ELISA for IL-13 levels.
  • Me-RIP and RIP assays for m6A methylation and protein-RNA interaction.

Main Results:

  • TIMMDC1 levels were elevated in asthma and promoted airway smooth muscle cell (ASMC) proliferation, migration, and M2 macrophage polarization.
  • METTL3 inhibited TIMMDC1 expression through m6A methylation.
  • Increased METTL3 expression suppressed ASMC proliferation, migration, and M2 macrophage polarization.

Conclusions:

  • METTL3 inhibits PDGF-BB-induced ASMC progression by downregulating TIMMDC1 expression.
  • This study provides novel molecular insights that may lead to new therapeutic strategies for asthma.
Keywords:
ASMCsAsthmaMETTL3TIMMDC1m6A methylation

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