Hyaluronan (HA) and HA-binding Proteins
Hyaluronan, also known as hyaluronic acid (HA) or sodium hyaluronate, is a naturally occurring linear polymer. Hyaluronan is a glycosaminoglycan (GAG) that is ubiquitously present in the extracellular matrix of all vertebrates and is also present in the capsule of some strains of Streptococci. Mammalian hyaluronan is synthesized by one of three distinct hyaluronan synthases (HAS1, 2, and 3), which produce HA polymers with different chain lengths and differ in their rates of synthesis. Whereas high molecular weight HA (> 500 kDa) is anti-angiogenic, anti-inflammatory and immunosuppressive, low molecular weight HA (10 - 500 kDa) is highly angiogenic and pro-inflammatory. HA oligomers are anti-apoptotic and upregulate heat shock protein expression. Functionally, hyaluronan molecules are important for the maintenance of a highly hydrated extracellular matrix in tissues, which is involved in cell adhesion and supports cell migration. Hyaluronan also exhibits diverse biological functions by interacting with a large number of hyaluronan-binding proteins and cell surface receptors, such as CD44 and LYVE-1.