Hepatocyte growth factor, keratinocyte growth factor, and other growth factor-receptor systems in the lens

Abstract

Purpose: To examine the expression and function of hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), epidermal growth factor (EGF) and other growth factor-cytokine-receptor systems in lens epithelial cells.

Methods: Reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis were used to examine the expression of messenger RNAs in primary cultured rabbit and human lens cells and in ex vivo rabbit lens tissue. Protein expression and the effect of HGF and KGF on crystallin expression in lens epithelial cells were evaluated by immunoprecipitation and Western blot analysis. The effect of exogenous HGF, KGF, and EGF and of the coculture of lens epithelial cells with corneal endothelial cells on the proliferation of rabbit lens cells in a Transwell system was determined by cell counting.

Results: Messenger RNAs and proteins of HGF and KGF were expressed in primary rabbit lens epithelial cells and in ex vivo rabbit lens epithelial tissue. Human lens cells also expressed the mRNAs. Other growth factors and receptor messenger RNAs were also expressed. Hepatocyte and keratinocyte growth factors, and coculture with corneal endothelial cells stimulated proliferation of rabbit lens epithelial cells. In first-passage rabbit lens cells, HGF, KGF, and EGF increased the expression of alpha and beta crystallins.

Conclusions: Hepatocyte and keratinocyte growth factor-receptor systems are expressed in lens cells. HGF and KGF are not expressed in epithelial cells in such tissues as skin, cornea, and lacrimal gland in which fibroblastic and epithelial cells interact in the formation of an organ. Expression of these growth factors in the lens may have evolved because the lens cells are relatively isolated within the anterior chamber of the eye. Our results suggest, however, that growth factors released by the corneal endothelium also could modulate lens functions (aquecrine interactions).