The role of laminin-5 in TGF alpha/EGF-mediated corneal epithelial cell motility.
Transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) stimulate corneal epithelial cell wound closure. However, the role of these growth factors in regulating corneal epithelial cell motility on basement membrane proteins such as laminin has not been elucidated. In the present study we demonstrate that in an in vitro model of corneal wound healing, TGF alpha has no deleterious effects on the deposition of the laminin-5 isoform into the extracellular matrix structure underlying epithelial cells resurfacing bare collagenous stroma. In primary culture, a population of corneal epithelial cells are stimulated by TGF alpha or EGF to become highly motile. These cells are associated with an endogenously secreted, and extracellularly deposited, 'trail' of laminin-5. The laminin-5 trail is specifically associated with motile cells, as non-motile corneal epithelium exhibiting numerous cell-cell contacts does not display a similar laminin-5 localization pattern. In contrast to these observations, a preparation of laminin-5 known to promote cell spreading, adhesion, and formation of hemidesmosomes, when presented exogenously to cultured corneal epithelial cells, does not stimulate motility. However, a commercially available preparation of laminin derived from human placenta which does not contain laminin-5 does significantly promote the migration of TGF alpha- or EGF-stimulated corneal epithelial cells. From these results, it is hypothesized that endogenously secreted laminin-5 functions to promote migration in corneal epithelial cells which have been treated with TGF alpha or EGF. Exogenously presented laminin-5 does not function similarly, but functions to promote corneal epithelial cell adhesion.
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Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Kurpakus
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D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D004815:Epidermal Growth Factor; D014409:Tumor Necrosis Factor-alpha; D000097794:Kalinin