NSUN2 promotes PM2.5-induced epithelial-mesenchymal transition through methylating chitinase 3-like-1 mRNA

J Hazard Mater. 2025 Sep 5:495:138883. doi: 10.1016/j.jhazmat.2025.138883. Epub 2025 Jun 9.

Abstract

Chitinase 3-like-1 (CHI3L1) is an emerging biomarker and therapeutic target for prediction and evaluation of respiratory diseases. However, the functions and underly molecular mechanisms on the regulation of CHI3L1 in PM2.5-induced pulmonary fibrosis are unclear. In the present study, we found that increased expressions of NSUN2 and the m5C methylation of CHI3L1 mRNA in PM2.5-treated lung tissues and alveolar epithelial MLE-12 cells were observed. NSUN2 could catalyze m5C methylation of CHI3L1 at the 3'UTR, thereby promoting the transport of CHI3L1 mRNA to cytoplasm in an Aly/REF export factor (ALYREF) dependent manner. Under PM2.5 exposure, NSUN2 deficiency could counterbalance PM2.5-induced CHI3L1 m5C methylation and epithelial-mesenchymal transition (EMT) in vivo and in cells. Our research collectively offers new molecular understanding regarding the mechanisms behind pulmonary fibrosis induced by PM2.5 exposure.

Keywords: CHI3L1; Methylation; NSUN2; PM(2.5); Pulmonary fibrosis.

MeSH terms

  • Animals
  • Cell Line
  • Chitinase-3-Like Protein 1* / genetics
  • Chitinase-3-Like Protein 1* / metabolism
  • Epithelial-Mesenchymal Transition* / drug effects
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Methylation
  • Methyltransferases* / genetics
  • Methyltransferases* / metabolism
  • Mice
  • Particulate Matter* / toxicity
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / metabolism
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism

Substances

  • Particulate Matter
  • RNA, Messenger
  • Chitinase-3-Like Protein 1
  • Methyltransferases
  • Chil1 protein, mouse