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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
- 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.
- Subjects :
- Glycobiology and Extracellular Matrices
Bronchi
Inflammation
Plasma protein binding
In Vitro Techniques
Biology
Biochemistry
Cell Line
Pathogenesis
Extracellular matrix
Mice
Alpha-Globulins
Pulmonary fibrosis
medicine
Animals
Humans
RNA, Messenger
Vitronectin
Lung
Molecular Biology
Mice, Knockout
Wound Healing
Binding Sites
Base Sequence
Epithelial Cells
Cell Biology
medicine.disease
Extracellular Matrix
Cell biology
Mice, Inbred C57BL
Immunology
Epithelial Metaplasia
biology.protein
medicine.symptom
Wound healing
Oligopeptides
Protein Binding
Subjects
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