Back to Search Start Over

Inter-α-trypsin Inhibitor Promotes Bronchial Epithelial Repair after Injury through Vitronectin Binding

Inter-α-trypsin Inhibitor Promotes Bronchial Epithelial Repair after Injury through Vitronectin Binding

Authors :
Masahiko Negishi
Lisheng Zhuo
Koji Kimata
Mack Sobhany
Vandy P. Stober
Stavros Garantziotis
Jennifer E. Adair
John Roberts
Source :
Journal of Biological Chemistry. 284:16922-16930
Publication Year :
2009
Publisher :
Elsevier BV, 2009.

Abstract

Pulmonary epithelial injury is central to the pathogenesis of many lung diseases, such as asthma, pulmonary fibrosis, and the acute respiratory distress syndrome. Regulated epithelial repair is crucial for lung homeostasis and prevents scar formation and inflammation that accompany dysregulated healing. The extracellular matrix (ECM) plays an important role in epithelial repair after injury. Vitronectin is a major ECM component that promotes epithelial repair. However, the factors that modify cell-vitronectin interactions after injury and help promote epithelial repair are not well studied. Inter-alpha-trypsin inhibitor (IaI) is an abundant serum protein. IaI heavy chains contain von Willebrand A domains that can bind the arginine-glycine-aspartate domain of vitronectin. We therefore hypothesized that IaI can bind vitronectin and promote vitronectin-induced epithelial repair after injury. We show that IaI binds vitronectin at the arginine-glycine-aspartate site, thereby promoting epithelial adhesion and migration in vitro. Furthermore, we show that IaI-deficient mice have a dysregulated response to epithelial injury in vivo, consisting of decreased proliferation and epithelial metaplasia. We conclude that IaI interacts not only with hyaluronan, as previously reported, but also other ECM components like vitronectin and is an important regulator of cellular repair after injury.

Details

ISSN :
00219258
Volume :
284
Database :
OpenAIRE
Journal :
Journal of Biological Chemistry
Accession number :
edsair.doi.dedup.....ec4c4d7ef07afb4a6a4c4bcc8d7ce332
Full Text :
https://doi.org/10.1074/jbc.m808560200