Increased Expression of Epidermal Growth Factor Receptor (EGF-R) in Patients with Different Forms of Lung Fibrosis

Abstract

Introduction. Emerging evidence supports the role of epidermal growth factor-receptor (EGFR) in fibrogenesis. The aim of our study was to investigate the expression profiles of EGFR in three forms of IIPs, including idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), and nonspecific interstitial pneumonia (NSIP). Patients and Methods. Twenty newly diagnosed patients with IPF, 15 with COP, and 15 with NSIP (cellular, n = 4 and fibrotic, n = 11) were investigated. Fifteen paraffin blocks obtained from the normal part of lungs removed for benign lesions were used as controls. Immunohistochemistry was carried out using specific monoclonal antibody. Results were verified by qRT-PCR. Results. A significant EGFR upregulation, both in protein and mRNA level, was observed in IPF, COP, and fibrotic NSIP samples compared to controls. EGFR was primarily localized in the hyperplastic alveolar epithelium surrounding areas of fibrosis in IPF, COP, and fibrotic NSIP samples, as assessed by double immunohistochemistry analysis with surfactant protein-A. EGFR mRNA levels were positively associated with indicators of lung fibrosis (type 1 collagen mRNA levels) and negatively correlated with functional prognostic parameters. Conclusions. We conclude that EGFR is upregulated in the hyperplastic alveolar epithelium in all three fibrotic forms of IIPs indicating a potential role during abnormal reepithelization.

Biogenesis of Lysosome-related Organelles Complex-1 Subunit 1 (BLOS1) Interacts with Sorting Nexin 2 and the Endosomal Sorting Complex Required for Transport-I (ESCRT-I) Component TSG101 to Mediate the Sorting of Epidermal Growth Factor Receptor into Endosomal Compartments

“…Increased expression of EGFR has been found in different types of lung fibrosis (40). It is unknown whether the lack of some HPS proteins would cause the impaired lysosomal degradation of EGFR in these patients, which may contribute to the development of lung fibrosis in their middle age.…”

Transforming Growth Factor Alpha is a Critical Mediator of Radiation Lung Injury

“…The lack of induction of EGF expression suggests that while EGFR may play a critical role in the radiation response of lungs, EGF does not. Indeed, a number of studies have shown an increase in expression or phosphorylation of EGFR after radiation exposure in lung or in the setting of lung fibrosis from a variety of causes (6, 7, 46). However, EGF expression was not reported in these studies.…”

“…Increased EGFR expression and activation have been described in a number of fibrotic lung pathologies, including radiation fibrosis (6, 7). Conversely, little is known about the expression of EGFR ligands in the setting of radiation lung injury.…”

Lung Tumor Suppressor GPRC5A Binds EGFR and Restrains Its Effector Signaling

“…Because aberrantly activated EGFR signaling is strongly associated with bronchial preneoplasia, inflammatory lungs in human (15), and in a mouse model of lung inflammation and lung cancer (16), it raises several questions: (i) why EGFR activation is regulatable in normal lung tissue whereas it is dysregulatable in inflammatory and precancerous lung tissues?…”