Abstract
Abstract: :
Purpose: To investigate the effects of various growth factors on the proliferation and death by apoptosis of human corneal epithelial cells. Methods: Transformed human corneal epithelial cells were incubated separately with 11 different growth factors implicated in the regulation of corneal function. Cell proliferation was evaluated by measurement of [3H]thymidine incorporation. Activation of the protein kinase Akt, which plays an important role in anti–apoptotic signaling, was assessed by immunoblot analysis with antibodies specific for a phosphorylated form of the enzyme. Apoptosis was quantitated by the terminal deoxyribonucleotidyl transferase–mediated dUTP–biotin nick–end labeling (TUNEL) assay. Results: Of the 11 growth factors examined, hepatocyte growth factor , insulin, insulin–like growth factor –1, –2, and epidermal growth factor each increased [3H]thymidine incorporation, elicited the activation of Akt, and inhibited the induction of apoptosis by sodium nitroprusside in human corneal epithelial cells. Transforming growth factor–ß1 and –ß2 inhibited [3H]thymidine incorporation but had no effect on Akt activity or on sodium nitroprusside–induced apoptosis in these cells. Platelet–derived growth factor–BB, basic fibroblast growth factor, keratinocyte growth factor, and nerve growth factor had no effects on the measured parameters. Conclusions: The growth factors examined can be classified into three groups on the basis of their effects on proliferation and apoptosis in human corneal epithelial cells. The growth factors that modulate these cellular functions may both contribute to maintenance of the corneal epithelium as well as coordinate the proliferative and apoptotic responses of this tissue.
Keywords: cornea: epithelium • apoptosis/cell death • cytokines/chemokines