Increased Expression of Gelatinase (MMP-2 and MMP-9) in Pterygia and Pterygium Fibroblasts with Disease Progression and Activation of Protein Kinase C

Abstract

To study the expression of matrix metalloprotease (MMP)-2 and MMP-9 mRNA and activities in various stages of surgically excised pterygium specimens and cultured pterygium fibroblasts and to study the effects of activation of protein kinase C (PKC) on the expression of these MMPs in pterygium fibroblasts. MMP-2 and MMP-9 mRNA expression and activities in 15 pterygium tissues and cultured pterygium fibroblasts were measured by RT-PCR and zymography. Five normal conjunctiva specimens and fibroblasts were tested as the controls. Changes of expression of MMP-2 and MMP-9 of fibroblasts after the simulation of a standard PKC activator, 2-O-tetradecanoyl-phorbol-13-acetate (TPA), were studied. MMP-2 and MMP-9 expression in pterygium tissues and fibroblasts was greater than those of normal tissues and fibroblasts and was closely relevant to the progression of pterygium. In early-stage pterygium tissues and cultured fibroblasts, MMP-9 was not expressed, activated MMP-2 could not be detected, and only a small amount of latent MMP-2 was present. In advanced-stage pterygium (pterygium head passed the papillary region), MMP-9 was expressed; activated MMP-2 and a large amount of latent MMP-2 could be detected in pterygium tissues and fibroblasts. TPA stimulated the expression of MMP-2 and MMP-9 by pterygium fibroblasts isolated from early-stage specimens in a dose-dependent manner. MMP-2 and MMP-9 expression by pterygium fibroblasts is significantly increased after the progression of pterygium. Activation of the PKC signaling pathway, aside from other previously reported signaling pathways, may play a role in the development and progression of pterygium.