Mechanisms of Pingchuan granules in inhibiting PANoptosis of airway epithelial cells through METTL3-mediated m6A modification of miR-29a-3p in the treatment of asthma
Objective:To observe the effect of Pingchuan granules on METTL3-mediated m6A modification of miR-29a-3p in airway epithelial cells,and to clarify its molecular mechanism in inhibiting airway inflammation of asthma.Methods:16HBE was induced by LPS(50 mg/L)to construct a cell model,and Pingchuan granules-containing serum and dexamethasone were given for intervention.The cell activity was detected by CCK8 assay,the content of inflammatory factors(TNF-α,IL-6 and IL-8)and the m6A modification level of miR-29a-3p were detected by ELISA,the expression of METTL3 and PAN-apoptotic protein was detected by Western blot and the expression of METTL3 and miR-29a-3p was detected by qRT-PCR,respectively.Results:Compared with the model group,Pingchuan granules could significantly increase the activity of 16HBE,inhibit the contents of in-flammatory factors TNF-α,IL-6 and IL-8,and downregulate PANoptosis-related proteins p-RIPK3,p-MLKL,cleaved Cas-pase-1,cleaved Caspase-3 and the ratio of GSDMD-NT/FL-GSDMD and GSDME-NT/FL-GSDME,the differences were sta-tistically significant(P<0.01).In addition,Pingchuan granules can significantly increase the expression levels of miR-29a-3p and METTL3 in 16HBE,and promote the m6A modification level of miR-29a-3p when compared with the model group,the differenc-es were statistically significant(P<0.01).Conclusion:Pingchuan granules enhance the m6A modification level of miR-29a-3p through METTL3,thereby inhibiting the PANoptosis of airway epithelial cells and improving airway inflammation.
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