IGF-1 released by corneal epithelial cells induces up-regulation of N-cadherin in corneal fibroblasts.

Interactions between epithelial cells and fibroblasts play important roles in tissue homeostasis. With the use of a coculture system in which human corneal fibroblasts and epithelial cells are cultured on opposite sides of a collagen (vitrigel) membrane, we have examined the effects of epithelial cells on expression of the adherens-junction protein N-cadherin in fibroblasts. Reverse transcription-polymerase chain reaction and immunoblot analyses showed that the presence of epithelial cells increased the expression of N-cadherin in fibroblasts at the mRNA and protein levels. This effect of epithelial cells was mimicked by insulin-like growth factor-1 (IGF-1) but not by epidermal growth factor or fibroblast growth factor. Depletion of IGF-1 in epithelial cells by RNA interference abolished the effect of these cells on N-cadherin expression in fibroblasts. The presence of epithelial cells activated the IGF-1 receptor as well as up-regulated expression of the transcriptional regulator ZEB1 in fibroblasts. RNA interference-mediated depletion of IGF-1 in epithelial cells prevented the effect of these cells on ZEB1 expression in fibroblasts. These results suggest that IGF-1 released from corneal epithelial cells up-regulates the expression of N-cadherin in corneal fibroblasts. Copyright 2009 Wiley-Liss, Inc.