NSUN2 promotes PM2.5-induced epithelial-mesenchymal transition through methylating chitinase 3-like-1 mRNA
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 PM<sub>2.5</sub>-induced pulmonary fibrosis are unclear. In the present study, we found that increased expressions of NSUN2 and the m<sup>5</sup>C methylation of CHI3L1 mRNA in PM<sub>2.5</sub>-treated lung tissues and alveolar epithelial MLE-12 cells were observed. NSUN2 could catalyze m<sup>5</sup>C 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 PM<sub>2.5</sub> exposure, NSUN2 deficiency could counterbalance PM<sub>2.5</sub>-induced CHI3L1 m<sup>5</sup>C 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 PM<sub>2.5</sub> exposure.
Authors
- Jingran Su (ORCID: https://orcid.org/0000-0002-9873-1770)
- Rulong Chen (ORCID: https://orcid.org/0000-0002-7714-5529)
- Yuanli Wang (ORCID: https://orcid.org/0000-0002-9685-1859)
- Fang Zhang (ORCID: https://orcid.org/0000-0003-4511-6659)
- Jingyi Li (ORCID: https://orcid.org/0000-0001-9763-500X)
- Chunjiang Li (ORCID: https://orcid.org/0009-0008-8157-5282)
- Wenjun Ding (ORCID: https://orcid.org/0000-0002-0233-0033)
- Yikun Tu
- Mengyao Shao
- Xiaotian Zhang (ORCID: https://orcid.org/0000-0003-1134-0775)
Institutions
- Beijing Normal University (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Journal of Hazardous Materials
- Published
- 2025-06-09
- DOI
- https://doi.org/10.1016/j.jhazmat.2025.138883
- Citations
- 1
- Primary Topic
- Studies on Chitinases and Chitosanases
- Type
- article
- Field-Weighted Citation Impact
- 0.81