Overview of Hyaluronan Science

Hyaluronan was isolated from the vitreous of bovine eyes in 1934 by Karl Meyer et al [1]. The vitreous is a clear and colorless jelly-like sphere with optical functions.

Hyaluronan is a unique molecule, because it is produced by species from a virus to a human being, and shows no difference in the molecular structure among species.

Hyaluronan exists ubiquitously in the body and is involved in a wide variety of physiological functions such as morphogenesis, cell proliferation/differentiation, cell death, immunity, inflammation, and neuronal activity.

Laurent et al. established the formula to calculate average molecular weight of hyaluronan [2]. 

Hascall and Heinegård showed how hyaluronan aggregated with proteoglycans in cartilage[3], leading research of hyaluronan binding proteins.

Toole showed that hyaluronan was implicated in morphogenesis [4], leading usage of hyaluronan in regenerative medicine.

DeAngelis et al. found the hyaluronan synthase of prokaryote in 1993 [5].

Itano and Kimata found the hyaluronan synthase of eukaryote in 1996 [6]. 

Camenisch et al. showed that hyaluronan synthase (Has2) (-/-) embryos lack hyaluronan exhibit severe cardiac and vascular abnormalities, and die during midgestation [7].

Hyaluronan has specific physical and physiological properties depending on its molecular weight ( see figure below).

Application of Hyaluronan

As a medical application of hyaluronan, Endre A. Balazs, M.D., Ph.D (www.matrixbiologyinstitute.org) developed a hyaluronan preparation for patients with osteoarthritis. Currently, it is applied to cataract surgery, dry eye, endoscopic surgery, skincare, hair care and so on.

A new strategy of Hyaluronan Science

Hyaluronan is now known to many people. However, its application is still very limited. At the forefront of hyaluronan research, it has been reported that naked mole rats showing longevity have ultra-high molecular weight hyaluronan to suppress cancer [8]. It is thought to be tips for longevity and cancer control. On the other hand, we found that HA4 small hyaluronan at the opposite end, leads to the growth of fertilized eggs, i.e., totipotent stem cells that are at the highest level of stem cells. HA4 will also contribute to infertility treatment and regenerative medicine by inducing longevity genes, sirtuins.

REFERENCES

1. THE POLYSACCHARIDE OF THE VITREOUS HUMOR. Karl Meyer and John W. Palmer.  J. Biol. Chem. 1934 107: 629-.
   
2. Fractionation of hyaluronic Acid. Laurent,Torvard.T. et al.,Biochemina et Biophysica Acta. 42,476-485(1960).
   
3. Aggregation of cartilage proteoglycans. III. Characteristics of the proteins isolated from trypsin digests of aggregates. Hascall and Heinegård.  Biol Chem. 1974 Jul 10;249(13):4250-6. ; Aggregation of cartilage proteoglycans. I. The role of hyaluronic acid. Hascall and Heinegård. J Biol Chem. 1974 Jul 10;249(13):4232-41. ; Aggregation of cartilage proteoglycans. II. Oligosaccharide competitors of the proteoglycan-hyaluronic acid interaction. Hascall and Heinegård. J Biol Chem. 1974 Jul 10;249(13):4242-9.
   
4. Hyaluronan in morphogenesis. Toole B. J Intern Med. 1997 Jul;242(1):35-40. Review. 
   
5. Molecular cloning, identification, and sequence of the hyaluronan synthase gene from group A Streptococcus pyogenes. DeAngelis PL, Papaconstantinou J, Weigel PH. J Biol Chem. 1993 Sep 15;268(26):19181-4.
6. Expression cloning and molecular characterization of HAS protein, a eukaryotic hyaluronan synthase. Itano N and Kimata K. J Biol Chem. 1996 Apr 26;271(17):9875-8.
   
7. Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme. Camenisch TD, Spicer AP, Brehm-Gibson T, Biesterfeldt J, Augustine ML, Calabro A Jr, Kubalak S, Klewer SE, McDonald JA. J Clin Invest. 2000 Aug;106(3):349-60.
8. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Tian X, Azpurua J, Hine C, Vaidya A, Myakishev-Rempel M, Ablaeva J, Mao Z, Nevo E, Gorbunova V, Seluanov A. Nature. 2013 Jul 18;499(7458):346-9.
   

Web sites of Hyaluronan Science

The International Society for Hyaluronan Sciences (ISHAS)

https://www.ishas.org

Hyaluronan Today

https://www.glycoforum.gr.jp/series/hyaluronanJ.html

The Matrix Biology Institute

https://www.matrixbiologyinstitute.org