Plasminogen activator inhibitor-1 (PAI-1) stimulates human corneal epithelial cell adhesion and migration in vitro.
In addition to its role as an inhibitor of urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) is hypothesized to regulate epithelial cell adhesion and migration. We have previously reported that PAI-1 may be an important regulatory factor of the uPA system in cornea. The purpose of this study was to extend those observations by determining the effect of exogenous PAI-1 on the migration and adhesion of human corneal epithelial cells (HCEC) in vitro. The expression of PAI-1 in non-transformed early passage HCEC was confirmed by immunofluorescence microscopy and Western blot analysis. Colorimetric assays coupled with function-inhibiting antibody studies using the matrix assembled in situ by cultured cells demonstrate that immobilized PAI-1 serves as an efficient substrate for HCEC adhesion. HCEC attachment to PAI-1 is comparable to that of laminin-10, a known strong adhesion protein for epithelial cells. In addition to serving as an adhesion substrate, PAI-1 also functions as a chemotactic agent for corneal epithelium. Additionally it promotes the random migration of HCEC, from an initial cell cluster, along a culture substrate. Our results in corneal epithelium are consistent with reports from other investigators showing that PAI-1 facilitates both epithelial adhesion and migration. From our studies we conclude that PAI-1 may play a dual role in corneal wound healing. Initially PAI-1 may function to stimulate migration and facilitate the reepithelialization of the wound bed. Post-reepithelization, PAI-1 may ensure corneal epithelial cell adhesion to matrix to promote successful wound healing.
Wang
Zhiyu
Z
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Sosne
Gabriel
G
Kurpakus-Wheater
Michelle
M
D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D019573:Epithelium, Corneal / Q000187:drug effects*; D005136:Eye Proteins / Q000032:analysis / Q000494:pharmacology; D006801:Humans; D007797:Laminin / Q000032:analysis; D008856:Microscopy, Fluorescence / Q000379:methods; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D005136:Eye Proteins; D007797:Laminin; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; C119013:laminin 10