EFFECT OF HYALURONAN ON MATRIX METALLOPROTEASE EXPRESSION IN FIBROBLASTS AND KERATOCYTES

ABSTRACT Both hyaluronan and matrix metalloproteases (MMPs) are thought to be involved in tissue remodelling in a variety of physiological and pathological processes such as embryonic development, morphogenesis, wound healing or tumor progression. Several cytokines and growth factors are involved in the regulation of the biosynthesis of hyaluronan and also of MMP-s. In order to explore the possible relationship between these processes we studied the effect of hyaluronan on MMP-s expression (biosynthesis and activation) in culture of human skin fibroblasts and corneal keratocytes (explant cultures and cell cultures). These cells were shown to exhibit distinct phenotypes as far as matrix biosynthesis is concerned. Using a synthetic substrate: N-Suc(ala) 3 pNA we measured elastase-type endopeptidase activity produced by fibroblasts and keratocytes and characterised the MMPs by zymography. Hyaluronan added to fibroblast as well as keratocytes cultures stimulated the membrane bound elastase type endopeptidase activity in a dose dependant fashion. In presence of 1 mg/ml of hyaluronan there was an increase of MMPs expression and also an activation of these MMPs both by fibroblasts and keratocytes.