Hyaluronan (also called hyaluronic acid or hyaluronate) is a glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is one of the chief components of the extracellular matrix, contributes significantly to cell proliferation and migration, and may also be involved in the progression of some malignant tumors. more...
Until the late 1970s, hyaluronan was described as a "goo" molecule, a ubiquitous carbohydrate polymer that comprised the extracellular matrix. For example, hyaluronan is a major component of the extracellular matrix that constitutes synovial fluid. Along with lubricin, it is one of the fluid's main lubricating components. It helps protect joints by increasing the viscosity of the fluid and by making the cartilage between bones more elastic.
While it is found in large numbers in extracellular matrices, hyaluronan also contributes to tissue hydrodynamics, movement and proliferation of cells, and participates in a number of cell surface receptor interactions, notably those including its primary receptor in vivo, CD44. Upregulation of CD44 itself is widely accepted as a marker of cell activation in lymphocytes.
Hyaluronan's contribution to tumor growth may be due to its interaction with CD44. CD44, the chief in vivo hyaluronan receptor, participates in cell adhesion interactions required by tumor cells. Some of the enzymes that break down hyaluronan are known tumor suppressants; paradoxically, the gene for hyaluronidase-2 is an oncogene and promotes tumor growth.
The chemical structure of hyaluronan was determined in the 1950s in the laboratory of Karl Meyer. Hyaluronan is a polymer of disaccharides themselves composed of D-glucuronic acid and D-N-acetylglucosamine, linked together via alternating beta-1,4 and beta-1,3 glycosidic bonds. Polymers of hyaluronan can range in size from 102 to 104 kDa in vivo.
Hyaluronan is energetically stable in part because of the stereochemistry of its component disaccharides. Bulky groups on each sugar molecule are in sterically favored positions while the smaller hydrogens assume the less favorable axial positions.
Hyaluronan is synthesized by a class of integral membrane proteins called hyaluronan synthases, of which vertebrates have three types: HAS1, HAS2, and HAS3. These enzymes lengthen hyaluronan by repeatedly adding glucuronic acid and N-acetylglucosamine to the nascent polysaccharide.
Hyaluronan is degraded by a family of enzymes called hyaluronidases. In humans, there are at least seven types of hyaluronidase-like enzymes, several of which are tumor suppressors. The degradation products of hyaluronan, the oligosaccharides and very low molecular weight hyaluronan, exhibit pro-angiogenic properties.
Hyaluronan is naturally found in many tissues of the body such as skin, cartilage, and the vitreous humor. It is therefore well suited to biomedical applications targeting these tissues. The first hyaluronan biomedical product, Healon, was developed in the 1970s and 1980s and is approved for use in ophthalmic surgery (i.e. corneal transplantation, cataract surgery, glaucoma surgery and retinal attachment surgery). Other biomedical companies also produce brands of hyaluronan for ophthalmic surgery .
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