WTAP-mediated m6A methylation stabilizes pIgR mRNA and attenuates smoke-induced epithelial inflammation and apoptosis
Related Experiment Video
Updated: Nov 2, 2026
Using Nicotine in a Silica-Exposed Mouse Model to Promote Lung Epithelial-Mesenchymal Transition
Published on: March 3, 2023
Jiaqi Li1,2, Shengyu Huang2, Guanghua Guo1
1Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Abstract:
Smoke inhalation injury (SII) dramatically elevates burn patient mortality. Although N6-methyladenosine (m6A) methylation is emerging as a central epitranscriptomic regulator of lung inflammation and injury, its specific involvement in SII remains unknown. Using an in vivo mouse SII model and smoke extract-treated MLE-12 cells, we show that smoke exposure downregulates the m6A writer-complex component WTAP and reduces global m6A methylation. WTAP knockdown attenuates epithelial inflammation, apoptosis, and STAT3 activation. Integrating transcriptomics with weighted gene co-expression network analysis (WGCNA) and MeRIP-qPCR, we identify pIgR as a downstream target: WTAP modifies m6A methylation within the 756/772 region of pIgR mRNA, and its knockdown prolongs pIgR mRNA half-life and elevates pIgR expression. pIgR silencing reverses the protection conferred by WTAP knockdown. These findings define a WTAP/m6A/pIgR axis that shapes the early epithelial response to smoke inhalation and identifies WTAP as a candidate therapeutic target for SII.
