METTL14 mediates SOCS1 mRNA m6A modification to regulate macrophage polarization to attenuate the mechanism of severe heat stroke lung injury

Abstract

Severe heat stroke is an acute pathological state triggered by high temperature, in which lung injury is a major complication and an important cause of high mortality. RNA N6-methyladenosine modification can affect macrophage polarization by regulating the stability and translation of mRNAs, which plays an important role in inflammation and tissue repair.

Methods

Establishment of severe heatstroke (HS) mice. Assessment of lung tissue changes using hematoxylin and eosin staining and immunohistochemical methods. CD206/iNOS/DAPI staining was used to detect the M1/M2 ratio. Real-time PCR was used to determine gene expression. Protein expression was determined by ELISA, Western blotting. Establishment of a heatstroke model in MH-S alveolar macrophages. Transcriptome sequencing analysis was performed to screen for differential genes, as well as expression of related signaling pathways.

Result

In vivo experiments have shown that severe pulmonary heatstroke caused an inflammatory response in lung tissue. RNA methylation modulators reduce lung tissue injury by decreasing macrophage expression while attenuating the expression of inflammatory factors. In vitro experiments showed that thermal shock significantly activated M1-type polarization in alveolar macrophages, induced activation of the NF-κB signaling pathway, and up-regulated the expression of the METTL14 gene and related inflammatory genes.

Conclusion

METTL14 significantly attenuates lung injury induced by severe heatstroke. This process is associated with its role in modulating the m6A modification of SOCS1 mRNA, which in turn affects the polarization state of macrophages and promotes the conversion from M1-to M2-type. This provides a new molecular target and theoretical basis for the treatment of severe heatstroke.