Fibroblast growth factor-2 promotes keratan sulfate proteoglycan expression by keratocytes in vitro

Keratocytes of the corneal stroma produce a specialized extracellular matri x responsible for corneal transparency. Corneal keratan sulfate proteoglyca ns (KSPG) are unique products of keratocytes that are down-regulated in cor neal wounds and in vitro. This study used cultures of primary bovine kerato cytes to define factors affecting KSPG expression in vitro. KSPG metabolica lly labeled with [S-35]sulfate decreased during the initial 2-4 days of cul ture in quiescent cultures with low serum concentrations (0.1%). Addition o f fetal bovine serum, fibroblast growth factor-2 (FGF-2), transforming grow th factor beta, or platelet derived growth factor all stimulated cell divis ion, but only FGF-2 stimulated KSPG secretion. Combined with serum, FGF-2 a lso prevented serum-induced KSPG down-regulation. KSPG secretion was lost d uring serial subculture with or without FGF-2, Expression of KSPG core prot eins (lumican, mimecan, and keratocan) was stimulated by FGF-2, and steady state mRNA pools for these proteins, particularly keratocan, were significa ntly increased by FGF-2 treatment. RSPG expression therefore is supported b y exogenous FGF-2 and eliminated by subculture of the cells in presence of serum. FGF-2 stimulates RSPG core protein expression primarily through an i ncrease in mRNA pools.