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.
Functions
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.
Structure
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.
Synthesis
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.
Degradation
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.
Medical applications
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 .
Hyaluronan is also used to treat osteoarthritis of the knee. Such
treatments are administered as a course of injections into the knee joint and
are believed to supplement the viscosity of the joint fluid thereby lubricating
the joint, cushioning the joint and producing an analgesic effect. It has also
been suggested that hyaluronan has positive biochemical effects on cartilage
cells. However, some placebo controlled studies have cast doubt on the efficacy
of hyaluronan injections and hyaluronan is recommended primarily as a last
alternative to surgery.
Since 2003 the FDA has approved hyaluronan injections for filling soft tissue
defects such as facial wrinkles These products are analogous to collagen
injections but have the advantages of longer lasting effects and decreased risk
of allergic reaction.
In some cancers, hyaluronan levels correlate well with malignancy and poor
prognosis. Hyaluronan is thus often used as a tumor marker for prostate and
breast cancer. It may also be used to monitor the progression of the disease.
Hyaluronan may also be used postoperatively to induce tissue healing, notably
after cataract surgery. Current models of wound healing propose that larger
polymers of hyaluronic acid appear in the early stages of healing to physically
make room for white blood cells, which mediate the immune response.
Hyaluronan is also now a common skin care ingredient.
The source of this article is
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