Sodium butyrate inhibits the proliferation and collagen gel contraction in keratocytes

Abstract

Abstract: : Purpose: Sodium butyrate (NaB), a histone deacetylase inhibitor, has been known to induce a G1 cell arrest, differentiation and apoptosis. In this study, to understand the role of NaB in the corneal wound healing process, we investigated the effect of NaB in the proliferation and the collagen gel contraction of keratocytes. Methods: Human keratocytes were seeded on 96–well culture plates and cultured in the serum–free MEM medium containing NaB(0.01–10mM) with or without TGF– ß (1ng/ml) or EGF(10ng/ml) for 24 hours. The cell numbers were measured by BrDU incorporation. In other experiment, keratocytes in collagen gels were cultured with the serum–free MEM medium containing NaB(0.03–3mM) with or without TGF–ß(1ng/ml) for 5 days and the gel diameters were measured. Results: NaB inhibited the proliferation of keratocytes in a dose dependent manner. The proliferation of keratocytes was stimulated by both TGF– ß and EGF. NaB inhibited the actions by both TGF– ß and EGF on keratocytes. NaB inhibited collagen gel contraction by keratocytes in a dose dependent manner. TGF–ß stimulated collagen gel contraction by keratocytes. NaB also antagonized the stimulatory effect of TGF– ß on the collagen gel contraction. Conclusions: These findings suggested that NaB may modulate corneal stromal wound healing by inhibiting the proliferation of keratocytes.

Keywords: cornea: stroma and keratocytes • proliferation • wound healing