Abstract
Hyaluronan (HA) is an unbranched glycosaminoglycan (GAG) which is the only nonsulfated disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine. HA is synthesized by most cells in various animal tissues and has by far the largest molecular size, with an average molecular weight of several million. HA plays important roles in tissue development, tissue hydration, cell surface-matrix interactions, cell migration, inflammation, and wound healing. The biosynthesis of HA is unique among the GAG. Rather than being made in the Golgi apparatus, HA is synthesized via HA synthase (HAS) which is located at the plasma membrane. Recently, it has been reported that 3 subtypes of HAS, named HAS 1, HAS 2 and HAS 3, have been cloned and that each of those plays a different role in HA production in vivo. Several lines of evidence demonstrated that expression of HAS and synthesis of HA are regulated by a variety of mechanisms other than cytokines and that the inducible HA production generates HA with relatively high molecular weight. Furthermore, recent observation demonstrated that HA with low molecular weight showed various biological activities such as induction of chemokines and iNOS. These data may suggest that HA plays crucial roles both in continuation of inflammatory responses and in restoration and maintenance of tissue homeostasis.
