Hyaluronan and HA-binding proteins

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Hyaluronan and HA-binding proteins

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Hyaluronan and HA-binding proteins Background

Hyaluronic acid, the basic structure is a large polysaccharide composed of two disaccharide units D-glucuronic acid and N-acetylglucosamine. Unlike other mucopolysaccharides, it does not contain sulfur. Its hyaluronic molecules can carry more than 500 times of water, which is the best moisturizing ingredient recognized today, and is widely used in skin care products and cosmetics. Hyaluronic acid is an acid mucopolysaccharide. In 1934, Meyer, a professor of ophthalmology at Columbia University in the United States, first isolated the substance from the vitreous of the bovine eye. Hyaluronic acid displays various important physiological functions in the body with its unique molecular structure and physicochemical properties, such as lubricating joints, regulating the permeability of blood vessel walls, regulating protein, water and electrolyte diffusion and operation, and promoting wound healing. Hyaluronic acid is a multifunctional substrate, and hyaluronic acid (hyaluronic acid) HA is widely distributed in various parts of the human body. The skin also contains a lot of hyaluronic acid. The process of human skin maturity and aging also changes with the content of hyaluronic acid and metabolism. It can improve the skin's nutrient metabolism, make the skin soft, smooth, wrinkle-free, increase elasticity, prevent aging, and at the same time be good at moisturizing. Skin absorption enhancer. Used in combination with other nutrients, it can promote the absorption of nutrients.

Skeletal formula of hyaluronan.Figure 1. Skeletal formula of hyaluronan.

Biological synthesis

Hyaluronic acid is synthesized from a class of intact membrane proteins called hyaluronan synthase, which has three types of vertebrate: HAS1, HAS2 and HAS3. These enzymes prolong hyaluronic acid by repeatedly adding glucuronic acid and N-acetylglucosamine to the nascent polysaccharide because it is extruded through the cell membrane into the extracellular space by the ABC transporter. The synthesis of hyaluronic acid has been inhibited by the 7-hydroxy-4-methylcoumarin derivative 4-methylumbelliferone (hydroxymethyl, heparin), this selective inhibition (does not inhibit other glycosaminoglycans) may prove to be useful for preventing metastasis of malignant cells. When tested in cultured human synovial fibroblasts, low concentrations of hyaluronic acid (<500 kDa) have a feedback inhibitory effect on hyaluronic acid synthesis at high concentrations, while high molecular weight (>500 kDa) HA stimulates hyaluronic acid Inhibition of synthesis. Bacillus subtilis has recently been genetically engineered to produce hyaluronic acid in a proprietary formulation and produced in a patented way to produce human-grade products.

Medical uses

Hyaluronic acid has been approved by the FDA for the treatment of knee osteoarthritis by injecting it into the joint, although a review suggests that the quality of the study is mostly poor and usually has no significant benefit, and intra-articular injection of hyaluronic acid may result in Serious adverse effects. Dry, scaly skin (for example, skin caused by atopic dermatitis) can be treated with a body lotion containing sodium hyaluronate as an active ingredient. Hyaluronic acid has been used in a variety of formulations to make artificial tears for the treatment of dry eye syndrome.

HA-binding proteins

To date, identified HA cell receptors fall into three broad categories: CD44, HA-mediated motor receptor, and intercellular adhesion molecule 1 (ICAM-1). Before the HA binding properties of CD44 and ICAM-1 were discovered, they have become cell adhesion molecules with other recognized ligands. CD44 is widely distributed throughout the body, and the official demonstration of HA-CD44 binding is proposed by Aruffo et al. In 1990. To date, it is considered to be the major cell surface receptor for HA. CD44 mediates the interaction of cells with HA, and the combination of these two functions is an important component of various physiological events (such as cell aggregation, migration, proliferation and activation); cell-to-cell and cell-to-matrix adhesion; HA Endocytosis, leading to HA catabolism in macrophages; assembly and assembly of pericellular matrices of HA and proteoglycans. Two important roles of CD44 in the skin have been proposed. The first is to regulate the proliferation of keratinocytes in response to extracellular stimuli, and the second is to maintain local HA homeostasis. ICAM-1 is primarily a metabolic cell surface receptor for HA, which may be responsible for the clearance of HA from lymph and plasma, which may be the main cause of its overall human renewal. Thus, ligand binding of the receptor triggers a highly coordinated event cascade, including the formation of endocytic vesicles, fusion with primary lysosomes, enzymatic digestion into monosaccharides, and transport of these sugars to the cytosol by transmembrane activity, Phosphorylation and enzymatic deacetylation of GlcNAc. Like its name, ICAM-1 can also act as a cell adhesion molecule, and binding of HA to ICAM-1 may help control ICAM-1 mediated inflammation activation.


1. Yoshihara S.; et al. A hyaluronan synthase suppressor, 4-methylumbelliferone, inhibits liver metastasis of melanoma cells. FEBS Lett. 579 (12): 2722–2726.

2. Yung S.; et al. Pathophysiology of the peritoneal membrane during peritoneal dialysis: the role of hyaluronan. J. Biomed. Biotechnol. 2011: 1–11.

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