ArticleAmerican journal of physiology. Heart and circulatory physiology2021
TNF-α-induced sympathetic excitation requires EGFR and ERK1/2 signaling in cardiovascular regulatory regions of the forebrain.
Article in American journal of physiology. Heart and circulatory physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
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- Epidermal growth factor receptor signaling modulates postoperative pain and inflammatory responses.Frontiers in immunology · 2026Review
- Impaired wound healing in Parkinson's disease: a hypothesis on altered epidermal growth factor (EGF) and N-methyl-D-aspartate (NMDA) signaling in keratinocytes.Molecular medicine (Cambridge, Mass.) · 2025Article
- Obesity- and High-Fat-Diet-Induced Neuroinflammation: Implications for Autonomic Nervous System Dysfunction and Endothelial Disorders.International journal of molecular sciences · 2025Review
- Low-intensity pulsed ultrasound elevates blood pressure for shock.Science advances · 2025Article
- Astragaloside IV Improves Cognitive Impairment by Reducing β-Amyloid and Tau Protein Deposition in Hippocampal Tissue of db/db Mice: A PET/CT Imaging-Based Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Tumor necrosis factor alpha induces NOX2-dependent reactive oxygen species production in hypothalamic paraventricular nucleus neurons following angiotensin II infusion.Neurochemistry international · 2024Article
- Activation AMPK in Hypothalamic Paraventricular Nucleus Improves Renovascular Hypertension Through ERK1/2-NF-κB Pathway.Cardiovascular toxicology · 2024Article
- Article
- Circulating mitochondria promoted endothelial cGAS-derived neuroinflammation in subfornical organ to aggravate sympathetic overdrive in heart failure mice.Journal of neuroinflammation · 2024Article
- The Anti-atherosclerosis Mechanism of Ziziphora clinopodioides Lam. Based On Network Pharmacology.Cell biochemistry and biophysics · 2023Article
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- Angiotensin II inhibits the A-type KAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2022Article
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- Reducing brain TACE activity improves neuroinflammation and cardiac function in heart failure rats.Frontiers in physiology · 2022Article
- Local ionotropic glutamate receptors are required to trigger and sustain ramping of sympathetic nerve activity by hypothalamic paraventricular nucleus TNFAmerican journal of physiology. Heart and circulatory physiology · 2021Article
- Article
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3 authors at 1 institution in 1 country.
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Abstract
Peripherally or centrally administered TNF-α elicits a prolonged sympathetically mediated pressor response, but the underlying molecular mechanisms are unknown. Activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in cardiovascular regions of the brain has recently been recognized as a key mediator of sympathetic excitation, and ERK1/2 signaling is induced by activation of epidermal growth factor receptor (EGFR) tyrosine kinase activity. The present study examined the role of EGFR and ERK1/2 signaling in the sympathetic response to TNF-α. In urethane-anesthetized rats, intracarotid artery injection of TNF-α increased phosphorylation of EGFR and ERK1/2 in the subfornical organ (SFO) and the hypothalamic paraventricular nucleus (PVN); upregulated the gene expression of excitatory mediators in SFO and PVN; and increased blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA). A continuous intracerebroventricular infusion of the selective EGFR tyrosine kinase inhibitor AG1478 or the ERK1/2 inhibitor PD98059 significantly attenuated these responses. Bilateral PVN microinjections of TNF-α also increased phosphorylated ERK1/2 and the gene expression of excitatory mediators in PVN, along with increases in BP, HR, and RSNA, and these responses were substantially reduced by prior bilateral PVN microinjections of AG1478. These results identify activation of EGFR in cardiovascular regulatory regions of the forebrain as an important molecular mediator of TNF-α-driven sympatho-excitatory responses and suggest that EGFR activation of the ERK1/2 signaling pathway plays an essential role. These mechanisms likely contribute to sympathetic excitation in pathophysiological states like heart failure and hypertension, in which circulating and brain TNF-α levels are increased.
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