EGFR Signaling in Lung Fibrosis

Abstract

In this review article, we will first provide a brief overview of the ErbB receptor–ligand system and its importance in developmental and physiological processes. We will then review the literature regarding the role of ErbB receptors and their ligands in the maladaptive remodeling of lung tissue, with special emphasis on idiopathic pulmonary fibrosis (IPF). Here we will focus on the pathways and cellular processes contributing to epithelial–mesenchymal miscommunication seen in this pathology. We will also provide an overview of the in vivo studies addressing the efficacy of different ErbB signaling inhibitors in experimental models of lung injury and highlight how such studies may contribute to our understanding of ErbB biology in the lung. Finally, we will discuss what we learned from clinical applications of the ErbB1 signaling inhibitors in cancer in order to advance clinical trials in IPF.

Systematic Analysis Strategy Based on Network Pharmacology to Investigate the Potential Mechanism of Fritillaria thunbergii Miq. against Idiopathic Pulmonary Fibrosis

“…On the basis of these findings, we speculate that ZBM can also exert antipulmonary fibrosis effects through the JAK/STAT signaling axis. Interestingly, the epidermal growth factor receptor (EGFR), a member of the ErbB tyrosine kinase receptor family, was shown to participate in wound healing and tissue regeneration by activating downstream PI3K/AKT, MAPK/ERK, and STAT signaling pathways [ 66 ]. In our study, we found that ZBM also significantly modulated the expression of EGFR and SRC, a nonreceptor tyrosine kinase that activates STAT3 and trans-activates EGFR.…”

Cloning a profibrotic stem cell variant in idiopathic pulmonary fibrosis

“…6, F and G). Given the evidence for aberrant EGFR signaling in lung fibrosis (50-52) and the differential expression of both EGFR receptors and ligands in the cluster B cells, the sensitivity of cluster B cells to EGFR inhibitors may provide a cellular mechanism for the efficacy of such drugs in model systems (51)(52)(53)(54)(55)(56).…”

State of the Art in Idiopathic Pulmonary Fibrosis

“…The contribution of airway epithelial cells to the development of IPF is supported by multiple lines of evidence, including the cellular composition and morphological alterations of IPF airways, strong associations between the MUC5B promoter rs35705950 polymorphism and the risk of IPF, and the bronchiolization of distal airspaces in IPF lungs. The contribution of airway epithelial cells to IPF pathogenesis is also addressed by Schramm et al, who discuss the role of the ErbB receptor–ligand system in lung fibrosis [ 15 ]. Intriguingly, the deregulation of the ErbB receptor-ligand axis is mainly observed in the regions of alveolar bronchiolization.…”

“…This underlies the pivotal role of ErbB receptors in the reprogramming of airway epithelial cells, and thereby honeycomb cyst formation and IPF progression. The authors of this comprehensive review emphasize the dual role of ErbB receptors and their ligands in lung fibrosis and indicate the need to elaborately characterize the dynamics and causal flows in the ErbB signaling networks in acute versus chronic lung injury [ 15 ].…”