Respiratory epithelial cell expression of human transforming growth factor-alpha induces lung fibrosis in transgenic mice.

Abstract

Increased production of EGF or TGF-a by the respiratory epi-

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

“…EGFR ligands can promote either proliferation or differentiation. It is proposed that ligands of the EGF family are released from the damaged epithelium and cause the proliferation of the underlying mesenchymal cells, as demonstrated in TGF-a transgene mice [38].…”

Mig-6is required for appropriate lung development and to ensure normal adult lung homeostasis

“…Overexpression of TGFα, an EGFR ligand, in the perinatal lung disrupts alveolarization and vascularization, leading to lung fibrosis in the adult (Korfhagen et al, 1994;Kramer et al, 2007;Le Cras et al, 2004;Le Cras et al, 2003). EGF can also activate the downstream signaling pathways RAS-PI3K/AKT and RAS/MAPK (Copland and Post, 2007;Kling et al, 2006;Uzumcu et al, 2002;Wang et al, 2005), and can cross-talk with other growth factors, such as TGFβ1 (Ding et al, 2007) and human growth hormone (HGF) signaling (Chess et al, 1998), all of which are important for lung development.…”

Amphiregulin, an Epidermal Growth Factor Receptor Ligand, Plays an Essential Role in the Pathogenesis of Transforming Growth Factor-β-induced Pulmonary Fibrosis

“…For example, increased expression of EGFR and TGF-␣, an EGFR ligand, were found in idiopathic pulmonary fibrosis patients and in the lungs of bleomycin-treated rats, an animal model of pulmonary fibrosis (18,19). TGF-␣ knock-out mice are protected from bleomycin-induced fibrosis whereas TGF-␣ over-expression in the murine lungs spontaneously induces progressive pulmonary fibrosis (20,21). The use of a selective EGFR tyrosine kinase inhibitor (Gefitinib) prevents the development of bleomycin-or TGF-␣-induced pulmonary fibrosis (22,23).…”