Downregulation of the Epidermal Growth Factor Receptor by Human Cytomegalovirus Infection in Human Fetal Lung Fibroblasts

2003 ◽  
Vol 28 (1) ◽  
pp. 86-94 ◽  
Author(s):  
Thomas Beutler ◽  
Conny Höflich ◽  
Paul A. Stevens ◽  
Detlev H. Krüger ◽  
Susanna Prösch
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cytomegalovirus Infection ◽  
Growth Factor Receptor ◽  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Epidermal Growth ◽  
Human Cytomegalovirus Infection ◽  
Human Fetal Lung

Mechanisms of human cytomegalovirus infection with a focus on epidermal growth factor receptor interactions

2017 ◽  
Vol 27 (6) ◽  
pp. e1955 ◽  
Author(s):  
Aline Semblano Carreira Falcão ◽  
Pedro Fernando da Costa Vasconcelos ◽  
Dorotéa de Fátima Lobato da Silva ◽  
João de Jesus Viana Pinheiro ◽  
Luiz Fábio Magno Falcão ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Human Cytomegalovirus ◽  
Cytomegalovirus Infection ◽  
Growth Factor Receptor ◽  
Receptor Interactions ◽  
Epidermal Growth ◽  
Human Cytomegalovirus Infection

scholarly journals Epidermal growth factor receptor paracrine upregulation in idiopathic pulmonary fibrosis fibroblasts is blocked by nintedanib

2019 ◽  
Vol 316 (6) ◽  
pp. L1025-L1034 ◽  
Author(s):  
Gali Epstein Shochet ◽  
Elizabetha Brook ◽  
Omer Eyal ◽  
Evgeny Edelstein ◽  
David Shitrit
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Growth Factor Receptor ◽  
Lung Fibroblasts ◽  
Fibroblast Growth ◽  
Egfr Expression ◽  
Epidermal Growth

Although present in normal cells, epidermal growth factor receptor (EGFR) is overexpressed in a variety of tumors and has been associated with decreased survival. Because activated fibroblasts are considered key effectors in fibrosis and because metastatic and fibrotic processes were shown to share similar signaling pathways, we investigated the contribution of EGFR signaling to idiopathic pulmonary fibrosis (IPF) progression in lung fibroblasts derived from patients with IPF (IPF-HLF). EGFR expression and EGFR-related signaling were evaluated by Western blot and immunohistochemistry. Supernatants (SN) from cultured IPF-HLF and N-HLF were added to N-HLF, and their effect on cell phenotype was tested. Growth factor levels in the SN were measured by ELISA-based arrays. EGFR activity was blocked by erlotinib (Tarceva, 0.1–0.5 µM). Expression of EGFR, phosphorylated (p)EGFR-1068 and pAkt-473 was significantly higher in IPF-HLF compared with lung fibroblasts from control donors (N-HLF) ( P < 0.05). Apparent expression of p/total EGFR and pAkt-473 was found in the myofibroblastic foci of IPF patients. Erlotinib significantly inhibited IPF-HLF but not N-HLF proliferation. IPF-HLF-SN elevated N-HLF cell number, viability, EGFR expression, and pAkt-473 and ERK1/2 phosphorylation ( P < 0.05). Because high basic fibroblast growth factor levels were found in the IPF-HLF-SN, nintedanib (10–100 nM) was used to inhibit fibroblast growth factor receptor (FGFR) activation. Unlike erlotinib, nintedanib completely blocked IPF-HLF-SNs’ effects on the N-HLF cells in a concentration-dependent manner. In summary, IPF-HLF paracrine signaling elevates EGFR expression, which in turn, affects N-HLF survival. The FGF-EGFR interplay facilitates cellular responses that could potentially promote fibrotic disease. This interplay was successfully blocked by nintedanib.

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