DNA 5mC and RNA m⁶A Collaborate to Upregulate Phosphoenolpyruvate Carboxykinase 2 for Kupffer Cell Activation.

ABSTRACT: Both DNA 5-methylcytosine (5mC) and RNA N6-methyladenosine (m⁶A) modifications are reported to participate in cellular stress responses including inflammation. Phosphoenolpyruvate carboxykinase 2 (PCK2) is upregulated in Kupffer cells (KCs) to facilitate the proinflammatory phosphorylation signaling cascades upon LPS stimulation, yet the role of 5mC and m⁶A in PCK2 upregulation remain elusive. Here, we report that the significantly augmented PCK2 mRNA and protein levels are associated with global 5mC demethylation coupled with m⁶A hypermethylation in LPS-activated KCs. The suppression of 5mC demethylation or m⁶A hypermethylation significantly alleviates the upregulation of PCK2 and proinflammatory cytokines in LPS-challenged KCs. Further reciproc

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC11432282 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature