Hyaluronan synthase: New directions for hyaluronan research

Abstract

Today, hyaluronan (hyaluronic acid) is known to be a polysaccharide widely present in most vertebrate tissues and in the capsule of certain streptococci strains. This macromolecule has further been used in various medical applications such as a supplement in the synovium of osteoarthritic joints, and its impotance is increasing yearly. Hyaluronan is a major component of extracellular matrix, especially in the tissues show high concentration in the molecule coinciding with periods of rapid cell proliferation and migration during embryogenesis. The interaction of hyaluronan with hyaluronan-binding protein and cell-surface receptors dynamically regulates many aspects of cell behavior such as cell adhesion, migration, and differentiation. Furthermore, this ubiquitous macromolecule is involved in many biological processes of morphogenesis, regeneration, wound healing, tumor invasion and cancer metastasis. On the other hand, trials to elucidate the hyaluronan biosynthetic mechanism and to identify a hyaluronan synthase have also been carried out as the main subject of hyaluronan research for past more than 10 years. Identification and molecular cloning of the hyaluronan synthase would shed new light upon questions of hyaluronan research. Recently, we and several other groups have succeeded in the molecular cloning of the prokaryotic and eukaryotic hyaluronan synthases, thereby the elucidation of hyaluronan biosynthetic mechanism and its biological functions are rapidly developing. This review highlights recent topics of hyaluronan synthase and points out the problems encountered in hyaluronan research. Finally, we will mention applications of hyaluronan synthase gene for elucidating the physiological functions of hyaluronan and clinical usage therefore.