Wound-induced TGF-β1 and TGF-β2 enhance airway epithelial repair via HB-EGF and TGF-α.

TitleWound-induced TGF-β1 and TGF-β2 enhance airway epithelial repair via HB-EGF and TGF-α.
Publication TypeJournal Article
Year of Publication2011
AuthorsIto, J, Harada, N, Nagashima, O, Makino, F, Usui, Y, Yagita, H, Okumura, K, Dorscheid, DR, Atsuta, R, Akiba, H, Takahashi, K
JournalBiochem Biophys Res Commun
Date Published2011 Aug 19
KeywordsCell Line, Heparin-binding EGF-like Growth Factor, Humans, Intercellular Signaling Peptides and Proteins, Phosphorylation, Receptor, Epidermal Growth Factor, Regeneration, Respiratory Mucosa, Transforming Growth Factor alpha, Transforming Growth Factor beta1, Transforming Growth Factor beta2

The abundance of transforming growth factor-beta (TGF-β) in normal airway epithelium suggests its participation in physiological processes to maintain airway homeostasis. The current study was designed to address the hypothesis that TGF-β1 and TGF-β2 might contribute to normal reparative response of airway epithelial cells (AECs). Treatments with exogenous TGF-β1 or TGF-β2 significantly enhanced wound repair of confluent AEC monolayers. Mechanical injury of AEC monolayers induced production of both TGF-β1 and TGF-β2. Wound repair of AECs was significantly reduced by a specific inhibitor of TGF-β type I receptor kinase activity. We investigated whether the TGF-β-enhanced repair required epidermal growth factor receptor (EGFR) transactivation and secretion of EGFR ligands. Both TGF-β1 and TGF-β2 enhanced EGFR phosphorylation and induced production of heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor-alpha (TGF-α) in AECs. Moreover, treatment with a broad-spectrum metalloproteinase inhibitor or anti-HB-EGF and anti-TGF-α antibodies inhibited the wound repair and the EGFR phosphorylation by TGF-β1 and TGF-β2, indicating that the TGF-β1 and TGF-β2 effects on wound repair required the release of HB-EGF and TGF-α. Our data, for the first time, have shown that both TGF-β1 and TGF-β2 play a stimulatory role in airway epithelial repair through EGFR phosphorylation following autocrine production of HB-EGF and TGF-α. These findings highlight an important collaborative mechanism between TGF-β and EGFR in maintaining airway epithelial homeostasis.

Alternate JournalBiochem. Biophys. Res. Commun.
PubMed ID21802406