Ets1-dependent Mek-Erk signaling drives adipose tissue macrophage anti-inflammatory polarization to ameliorates insulin resistance - PubMed
4 hours ago
- #Erk signaling
- #macrophage polarization
- #insulin resistance
- Mek-Erk inhibitors have paradoxical immunoregulatory effects on macrophages, with unclear mechanisms for specific outputs.
- Ets1 is identified as a discriminative effector that specifically links Mek-Erk signaling to anti-inflammatory macrophage polarization.
- Only IL-4, not other stimuli, activates Ets1's transcriptional activity via Thr38 phosphorylation, while pro-inflammatory conditions leave it inactive.
- Myeloid-specific Ets1 knockout exacerbates adipose inflammation and metabolic dysfunction in both physiological and obesity conditions.
- Ets1 upregulates Irf4 expression through transcriptional regulation and chromatin remodeling, driving anti-inflammatory polarization in macrophages.
- The bifurcated activation of Erk signaling via Ets1 enables macrophage functional specialization based on upstream stimuli.