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

被引：22
|
作者：
Ito, Jun [2 ,3 ]
Harada, Norihiro [1 ,2 ,3 ]
Nagashima, Osamu [2 ]
Makino, Fumihiko [2 ,3 ]
Usui, Yoshihiko [3 ,5 ]
Yagita, Hideo [3 ]
Okumura, Ko [3 ,4 ]
Dorscheid, Delbert R. [6 ]
Atsuta, Ryo [2 ]
Akiba, Hisaya [3 ]
Takahashi, Kazuhisa [2 ]
机构：
[1] Juntendo Univ, Sch Med, Dept Resp Med, Bunkyo Ku, Tokyo 1138421, Japan
[2] Juntendo Univ, Sch Med, Res Inst Dis Old Ages, Tokyo 1138421, Japan
[3] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 1138421, Japan
[4] Juntendo Univ, Sch Med, Atopy Allergy Res Ctr, Tokyo 1138421, Japan
[5] Tokyo Med Univ, Dept Ophthalmol, Tokyo, Japan
[6] Univ British Columbia, Providence Heart Lung Inst, UBC James Hogg Res Ctr, Vancouver, BC V5Z 1M9, Canada
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2011年 / 412卷 / 01期
关键词：
Bronchial epithelial cell; Epithelial repair; Transforming growth factor-beta; Heparin-binding EGF-like growth factor; Transforming growth factor-alpha; GROWTH-FACTOR-BETA; FACTOR RECEPTOR; IN-VITRO; EXPRESSION; CELLS; INVOLVEMENT; ACTIVATION; PROLIFERATION;
D O I：
10.1016/j.bbrc.2011.07.054
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The abundance of transforming growth factor-beta (TGF-beta) 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-beta 1 and TGF-beta 2 might contribute to normal reparative response of airway epithelial cells (AECs). Treatments with exogenous TGF-beta 1 or TGF-beta 2 significantly enhanced wound repair of confluent AEC monolayers. Mechanical injury of AEC monolayers induced production of both TGF-beta 1 and TGF-beta 2. Wound repair of AECs was significantly reduced by a specific inhibitor of TGF-beta type I receptor kinase activity. We investigated whether the TGF-beta-enhanced repair required epidermal growth factor receptor (EGFR) transactivation and secretion of EGFR ligands. Both TGF-beta 1 and TGF-beta 2 enhanced EGFR phosphorylation and induced production of heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor-alpha (TGF-alpha) in AECs. Moreover, treatment with a broad-spectrum metalloproteinase inhibitor or anti-HB-EGF and anti-TGF-alpha antibodies inhibited the wound repair and the EGFR phosphorylation by TGF-beta 1 and TGF-beta 2, indicating that the TGF-beta 1 and TGF-beta 2 effects on wound repair required the release of HB-EGF and TGF-alpha. Our data, for the first time, have shown that both TGF-beta 1 and TGF-beta 2 play a stimulatory role in airway epithelial repair through EGFR phosphorylation following autocrine production of HB-EGF and TGF-alpha. These findings highlight an important collaborative mechanism between TGF-beta and EGFR in maintaining airway epithelial homeostasis. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码：109 / 114
页数：6
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