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

J Biol Chem. 2000 May 5;275(18):13918-23. doi: 10.1074/jbc.275.18.13918.


Keratocytes of the corneal stroma produce a specialized extracellular matrix responsible for corneal transparency. Corneal keratan sulfate proteoglycans (KSPG) are unique products of keratocytes that are down-regulated in corneal wounds and in vitro. This study used cultures of primary bovine keratocytes to define factors affecting KSPG expression in vitro. KSPG metabolically labeled with [(35)S]sulfate decreased during the initial 2-4 days of culture in quiescent cultures with low serum concentrations (0.1%). Addition of fetal bovine serum, fibroblast growth factor-2 (FGF-2), transforming growth factor beta, or platelet derived growth factor all stimulated cell division, but only FGF-2 stimulated KSPG secretion. Combined with serum, FGF-2 also prevented serum-induced KSPG down-regulation. KSPG secretion was lost during serial subculture with or without FGF-2. Expression of KSPG core proteins (lumican, mimecan, and keratocan) was stimulated by FGF-2, and steady state mRNA pools for these proteins, particularly keratocan, were significantly increased by FGF-2 treatment. KSPG expression therefore is supported by exogenous FGF-2 and eliminated by subculture of the cells in presence of serum. FGF-2 stimulates KSPG core protein expression primarily through an increase in mRNA pools.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Cells, Cultured
  • Chondroitin Sulfate Proteoglycans / biosynthesis*
  • Cornea / metabolism*
  • Down-Regulation
  • Fibroblast Growth Factor 2 / pharmacology*
  • Keratan Sulfate / biosynthesis*
  • Lumican
  • Stromal Cells / metabolism
  • Up-Regulation


  • Chondroitin Sulfate Proteoglycans
  • Lumican
  • Fibroblast Growth Factor 2
  • Keratan Sulfate