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

  • 0Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
Journal of hazardous materials +

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June 14, 2025

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.

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