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

Abstract 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. J. Cell. Physiol. 221: 254–261, 2009. © 2009 Wiley‐Liss, Inc