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hyaluronic acid

Sunday 5 February 2006

Hyaluronan

Definition: Hyaluronan (also called hyaluronic acid or hyaluronate) is a non-sulfated 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.

The average 70 kg (154 lbs) person has roughly 15 grams of hyaluronan in their body, one-third of which is turned over (degraded and synthesised) every day.

Hyaluronan is a rapidly turned over component of the vertebrate extracellular matrix. Its levels are determined, in part, by the hyaluronan synthases, HAS1, HAS2, and HAS3, and three hyaluronidases, HYAL1, HYAL2 and HYAL3.

Hyaluronan binding proteins also regulate hyaluronan levels although their involvement is less well understood.

Pathology

To date, two genetic disorders of hyaluronan metabolism have been reported in humans:
- HYAL1 deficiency (Mucopolysaccharidosis IX) in four individuals with joint pathology as the predominant phenotypic finding
- HAS2 deficiency in a single person having cardiac pathology.

However, inherited disorders and induced mutations affecting hyaluronan metabolism have been characterized in other species.

Overproduction of hyaluronan by HAS2 results in skin folding and thickening in shar-pei dogs and the naked mole rat, whereas a complete deficiency of HAS2 causes embryonic lethality in mice due to cardiac defects.

Deficiencies of murine HAS1 and HAS3 result in a predisposition to seizures. Like humans, mice with HYAL1 deficiency exhibit joint pathology.

Mice lacking HYAL2 have variably penetrant developmental defects, including skeletal and cardiac anomalies.

Thus, based on mutant animal models, a partial deficiency of HAS2 or HYAL2 might be compatible with survival in humans, while complete deficiencies of HAS1, HAS3, and HYAL3 may yet be recognized.

Function

Hyaluronic acid is also a component of the group A streptococcal extracellular capsule, and is believed to play a role in virulence.

Hyaluronic acid is an abundant extracellular matrix glycosaminoglycan (GAG) in skin and mesenchymal tissues, where it facilitates cell migration during wound healing, inflammation, and embryonic morphogenesis.

HA is a polysaccharide of the glycosaminoglycans (GAG) family found in the extracellular matrix (ECM) of many tissues. HA is a huge molecule that consists of many repeats of a simple disaccharide stretched end-to-end. HA binds a large amount of water, forming a viscous hydrated gel that gives connective tissue the ability to resist compression forces.

HA helps provide resilience and lubrication to many types of connective tissue, notably for the cartilage in joints. HA is also found in the matrix of migrating and proliferating cells, where it inhibits cell-to-cell adhesion and facilitates cell motility.

Ligands

CD44 a surface glycoprotein expressed by leukocytes, binds HA. Through such binding, T cells may be retained in tissues and remain bound to endothelium at sites of inflammation.

Pathology

- Hyaluronan 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.

- Hyaluronic acid is also a component of the group A streptococcal extracellular capsule, and is believed to play a role in virulence.

See also

- glycosaminoglycans (GAGs)
- extracellular matrix (ECM)

Open references

- Biology of hyaluronan: Insights from genetic disorders of hyaluronan metabolism. Triggs-Raine B, Natowicz MR. World J Biol Chem. 2015 Aug 26;6(3):110-20. doi : 10.4331/wjbc.v6.i3.110 Review. PMID: 26322170 (Free)

References

- Toole BP. Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer. 2004 Jul;4(7):528-39. PMID: 15229478

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