TNF-α-induced sympathetic excitation requires EGFR and ERK1/2 signaling in cardiovascular regulatory regions of the forebrain
Shun‐Guang Wei, Yang Yu, Robert B. Felder
Abstract
Proinflammatory cytokines contribute to the augmented sympathetic nerve activity in hypertension and heart failure, but the central mechanisms involved are largely unknown. The present study reveals that TNF-α transactivates EGFR in the subfornical organ and the hypothalamic paraventricular nucleus to initiate ERK1/2 signaling, upregulate the gene expression of excitatory mediators, and increase sympathetic nerve activity. These findings identify EGFR as a gateway to sympathetic excitation and a potential target for intervention in cardiovascular disease states.
Topics & Concepts
Internal medicineEndocrinologyForebrainMedicineExcitatory postsynaptic potentialTyrosine kinaseSignal transductionReceptorBiologyCell biologyCentral nervous systemNeuroscience of respiration and sleepNeuroendocrine regulation and behaviorStress Responses and Cortisol