TGF-β regulates m 6 A RNA methylation after PM 2.5 exposure

Abstract Atmospheric particulate matter exposure has adverse effects on human health, but its molecular mechanism is complex and need to be explored in depth over time. m 6 A RNA methylation is an important epigenetic modification that regulates gene expression at the post-transcriptional level. Our previous animal exposure studies found that PM 2.5 exposure up-regulated m 6 A RNA methylation in lung, but the regulatory pathway is currently unclear. PM 2.5 can activate transforming growth factor-β (TGF-β), and Smad2/3, a downstream factor of TGF-β, can affect m 6 A RNA methylation by binding to the RNA methyltransferase complex. Based on the above evidences, the current study aimed to investigate the role of TGF-β signal pathway in PM 2.5 -induced m 6 A RNA methylation through animal and A549 cell exposure model. Our results showed that PM 2.5 could induce upregulation of m 6 A RNA methylation, accompanied by increased expression of TGF-β, Smad3, methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14) in both lungs of mice and A549 cell line. Furthermore, the TGF-β inhibition cellular experiments determined that PM 2.5 exposure altered the level of m 6 A RNA methylation, expression of TGF-β, Smad3. Accordingly, it is clear that TGF-β plays an indispensable role in m 6 A RNA methylation after PM 2.5 exposure. Our study demonstrates that PM 2.5 exposure influence RNA m 6 A methylation through the TGF-β signal pathway.