Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Mar 22;22(6):3204.
doi: 10.3390/ijms22063204.

Hyaluronidases in Human Diseases

Aditya Kaul  1   2 , Walker D Short  1   2 , Xinyi Wang  1   2 , Sundeep G Keswani  1   2
Affiliations
Review

Hyaluronidases in Human Diseases

Aditya Kaul et al. Int J Mol Sci. .

Abstract

With the burgeoning interest in hyaluronic acid (HA) in recent years, hyaluronidases (HYALs) have come to light for their role in regulating catabolism of HA and its molecular weight (MW) distribution in various tissues. Of the six hyaluronidase-like gene sequences in the human genome, HYALs 1 and 2 are of particular significance because they are the primary hyaluronidases active in human somatic tissue. Perhaps more importantly, for the sake of this review, they cleave anti-inflammatory and anti-fibrotic high-molecular-weight HA into pro-inflammatory and pro-fibrotic oligosaccharides. With this, HYALs regulate HA degradation and thus the development and progression of various diseases. Given the dearth of literature focusing specifically on HYALs in the past decade, this review seeks to expound their role in human diseases of the skin, heart, kidneys, and more. The review will delve into the molecular mechanisms and pathways of HYALs and discuss current and potential future therapeutic benefits of HYALs as a clinical treatment.

Keywords: disease; hyaluronic acid; hyaluronidase; molecular weight.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic illustration depicting the chromosomal locations of hyaluronidases (HYALs) 1–6 and a secreted HYAL enzyme cleaving hyaluronic acid (HA). HYALs 1–3 are located on chromosome loci 3p21.3, and HYALs 4–6 on 7q31.3. Hyaluronidases are involved in the constant turnover of the extracellular proteoglycan hyaluronan, generating fragments of various molecular weights depending on the type of hyaluronidase. Pictured here is an extracellular hyaluronidase degrading HA, although it is important to note that HYAL may reside inside endosomes or be bound to the membrane surface. This figure is a broad illustration and is not drawn to scale. Created with BioRender.com.
See this image and copyright information in PMC

References

    1. Meyer K., Palmer J.W. The polysaccharide of the vitreous humor. J. Biol. Chem. 1934;107:629–634. doi: 10.1016/S0021-9258(18)75338-6. - DOI
    1. Nagy N., Sunkari V.G., Kaber G., Hasbun S., Lam D.N., Speake C., Sanda S., McLaughlin T.L., Wight T.N., Long S.R., et al. Hyaluronan levels are increased systemically in human type 2 but not type 1 diabetes independently of glycemic control. Matrix Biol. 2019;80:46–58. doi: 10.1016/j.matbio.2018.09.003. - DOI - PMC - PubMed
    1. Wang C.T., Lin Y.T., Chiang B.L., Lin Y.H., Hou S.M. High molecular weight hyaluronic acid down-regulates the gene expression of osteoarthritis-associated cytokines and enzymes in fibroblast-like synoviocytes from patients with early osteoarthritis. Osteoarthr. Cartil. 2006;14:1237–1247. doi: 10.1016/j.joca.2006.05.009. - DOI - PubMed
    1. Inokoshi Y., Tanino Y., Wang X., Sato S., Fukuhara N., Nikaido T., Fukuhara A., Saito J., Frevert C.W., Munakata M. Clinical significance of serum hyaluronan in chronic fibrotic interstitial pneumonia. Respirology. 2013;18:1236–1243. doi: 10.1111/resp.12144. - DOI - PubMed
    1. Duran-Reynals F. The effect of extracts of certain organs from normal and immunized animals on the infecting power of vaccine virus. J. Exp. Med. 1929;50:327–340. doi: 10.1084/jem.50.3.327. - DOI - PMC - PubMed