Plasminogen activators in human corneal fibroblasts: secretion, cellular localization, and regulation

Plasminogen activators (PA) play an important role not only in fibrinolysis but also in a variety of processes including tissue remodelling. The stroma of the cornea is a dense connective tissue characterized by its transparency. Healing, degenerative, and inflammatory processes lead to corneal opacification. In an attempt to determine the role of PA in corneal physiology, we have analysed the secretion of PA and plasminogen activator inhibitor (PAI-1) by corneal fibroblasts in vitro. We show that in contrast to other adult fibroblasts, corneal fibroblasts secrete both tissue-type plasminogen activator (t-PA) and urokinase-plasminogen activator (u-PA). Epithelial growth factor and basic fibroblast growth factor stimulated t-PA secretion whereas transforming growth factor-β decreased t-PA and increased PAI-1 secretion. t-PA was secreted in the surrounding medium while u-PA remained mostly associated to the cell surface. The production and secretion of t-PA are characteristic of corneal fibroblasts and could be implicated in matrix remodelling and the maintenance of corneal transparency.