Format

Send to

Choose Destination
See comment in PubMed Commons below
Am J Respir Cell Mol Biol. 2004 Dec;31(6):672-8. Epub 2004 Aug 12.

Plasminogen activator inhibitor-1 impairs alveolar epithelial repair by binding to vitronectin.

Author information

1
Department of Internal Medicine, University of Michigan Medical Center, 1150 West Medical Center Drive, 6301 MSRB III, Ann Arbor, MI 48109-0642, USA.

Abstract

The pathogenesis of pulmonary fibrosis is thought to involve alveolar epithelial injury that, when successfully repaired, can limit subsequent scarring. The plasminogen system participates in this process with the balance between urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) being a critical determinant of the extent of collagen accumulation that follows lung injury. Because the plasminogen system is known to influence the rate of migration of epithelial cells, including keratinocytes and bronchial epithelial cells, we hypothesized that the balance of uPA and PAI-1 would affect the efficiency of alveolar epithelial cell (AEC) wound repair. Using an in vitro model of AEC wounding, we show that the efficiency of repair is adversely affected by a deficiency in uPA or by the exogenous administration of PAI-1. By using PAI-1 variants and AEC from mice transgenically deficient in vitronectin (Vn), we demonstrate that the PAI-1 effect requires its Vn-binding activity. Furthermore, we have found that cell motility is enhanced by the availability of Vn in the matrix and that the AEC-Vn interaction is mediated, in part, by the alpha(v)beta(1) integrin. The significant effect of uPA and PAI-1 on epithelial repair suggests a mechanism by which the plasminogen system may modulate pulmonary fibrosis.

PMID:
15308506
DOI:
10.1165/rcmb.2004-0025OC
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon Icon for MLibrary (Deep Blue)
    Loading ...
    Support Center