ArticleFree radical biology & medicine2016
Redox regulation of epidermal growth factor receptor signaling during the development of pulmonary hypertension.
Article in Free radical biology & medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Lung Single-Cell Transcriptomics Reveal Diverging Pathobiology and Opportunities for Precision Targeting in Scleroderma-Associated Versus Idiopathic Pulmonary Arterial Hypertension.Circulation. Genomic and precision medicine · 2025Article
- Restoration of pp60International journal of molecular sciences · 2025Article
- Glucose-6-Phosphate Dehydrogenase, Redox Homeostasis and Embryogenesis.International journal of molecular sciences · 2022Review
- The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy.Biology · 2022Article
- Redox Regulation, Oxidative Stress, and Inflammation in Group 3 Pulmonary Hypertension.Advances in experimental medicine and biology · 2021Review
- Necrosis-Released HMGB1 (High Mobility Group Box 1) in the Progressive Pulmonary Arterial Hypertension Associated With Male Sex.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Altered Lipid Domains Facilitate Enhanced Pulmonary Vasoconstriction after Chronic Hypoxia.American journal of respiratory cell and molecular biology · 2020Article
- Early progression of pulmonary hypertension in the monocrotaline model in males is associated with increased lung permeability.Biology of sex differences · 2020Article
- Inhibition of Anaplerosis Attenuated Vascular Proliferation in Pulmonary Arterial Hypertension.Journal of clinical medicine · 2020Article
- Antioxidant-Conjugated Peptide Attenuated Metabolic Reprogramming in Pulmonary Hypertension.Antioxidants (Basel, Switzerland) · 2020Article
- Src and Epidermal Growth Factor Receptor: Novel Partners in Mediating Chronic Hypoxia-induced Pulmonary Artery Hypertension.American journal of respiratory cell and molecular biology · 2020Article
- Augmented Pulmonary Vasoconstrictor Reactivity after Chronic Hypoxia Requires Src Kinase and Epidermal Growth Factor Receptor Signaling.American journal of respiratory cell and molecular biology · 2020Article
- Gender Difference in Damage-Mediated Signaling Contributes to Pulmonary Arterial Hypertension.Antioxidants & redox signaling · 2019Article
- Focus on Early Events: Pathogenesis of Pulmonary Arterial Hypertension Development.Antioxidants & redox signaling · 2019Review
- Redox Regulation of Ion Channels and Receptors in Pulmonary Hypertension.Antioxidants & redox signaling · 2019Review
- Role of Gender in Regulation of Redox Homeostasis in Pulmonary Arterial Hypertension.Antioxidants (Basel, Switzerland) · 2019Review
- Inositol monophosphatase 1 as a novel interacting partner of RAGE in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- BRET-based assay to monitor EGFR transactivation by the ATBiochemical pharmacology · 2018Article
- Hypoxic-induction of arginase II requires EGF-mediated EGFR activation in human pulmonary microvascular endothelial cells.Physiological reports · 2018Article
- Endothelial cell signaling and ventilator-induced lung injury: molecular mechanisms, genomic analyses, and therapeutic targets.American journal of physiology. Lung cellular and molecular physiology · 2017Review
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The development of pulmonary hypertension (PH) involves the uncontrolled proliferation of pulmonary smooth muscle cells via increased growth factor receptor signaling. However, the role of epidermal growth factor receptor (EGFR) signaling is controversial, as humans with advanced PH exhibit no changes in EGFR protein levels and purpose of the present study was to determine whether there are post-translational mechanisms that enhance EGFR signaling in PH. The EGFR inhibitor, gefinitib, significantly attenuated EGFR signaling and prevented the development of PH in monocrotaline (MCT)-exposed rats, confirming the contribution of EGFR activation in MCT induced PH. There was an early MCT-mediated increase in hydrogen peroxide, which correlated with the binding of the active metabolite of MCT, monocrotaline pyrrole, to catalase Cys377, disrupting its multimeric structure. This early oxidative stress was responsible for the oxidation of EGFR and the formation of sodium dodecyl sulfate (SDS) stable EGFR dimers through dityrosine cross-linking. These cross-linked dimers exhibited increased EGFR autophosphorylation and signaling. The activation of EGFR signaling did not correlate with pp60(src) dependent Y845 phosphorylation or EGFR ligand expression. Importantly, the analysis of patients with advanced PH revealed the same enhancement of EGFR autophosphorylation and covalent dimer formation in pulmonary arteries, while total EGFR protein levels were unchanged. As in the MCT exposed rat model, the activation of EGFR in human samples was independent of pp60(src) phosphorylation site and ligand expression. This study provides a novel molecular mechanism of oxidative stress stimulated covalent EGFR dimerization via tyrosine dimerization that contributes into development of PH.
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