Investigation of the Difference in Growth-Promoting Factor Secretion Between Canine and Rabbit Corneal Epithelial Cells.

Abstract

OBJECTIVE: We hypothesized that canine corneal epithelial cells maintain their proliferative properties through autocrine secretion of growth-promoting factors. This study aimed to investigate the maintenance mechanism of the proliferative properties of canine corneal epithelial cells by comparing the autocrine secretion of soluble factors in canine and rabbit corneal epithelial cells. PROCEDURES: The effect of conditioned medium from primary canine corneal epithelial cells and canine corneal epithelial cell line (cCEpi) on the growth of rabbit corneal epithelial cells was evaluated, and vice versa. cDNA microarray and quantitative polymerase chain reaction analyses were performed, and the gene expression of soluble factors in canine and rabbit corneal epithelial cells was compared. RESULTS: Conditioned media of cCEpi cells significantly increased rabbit cell growth, but that of rabbit corneal epithelial cells significantly inhibited the growth of canine corneal epithelial cells and cCEpi cells. Epidermal growth factor (EGF) receptor ligands, including neuregulin 1 (NRG1) and heparin-binding EGF-like growth factor (HB-EGF), were highly expressed in canine corneal epithelial cells and cCEpi. In contrast, high expression of soluble factors related to transforming growth factor-β (TGF-β) signaling, including connective tissue growth factor (CTGF) and TGF-β2, was observed in rabbit corneal epithelial cells. CONCLUSIONS: Canine corneal epithelial cells secrete growth-promoting factors such as NRG1 and HB-EGF in an autocrine manner and have a low potential to secrete growth inhibitory factors such as CTGF and TGF-β2. These mechanisms would play important roles in the maintenance of the proliferative properties of canine corneal epithelial cells.