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Journal of Biochemistry Advance Access published online on April 4, 2008
Journal of Biochemistry, doi:10.1093/jb/mvn046
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© 2008 The Japanese Biochemical Society

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Simple Structure, Complex Turnover Regulation, and Multiple Roles of Hyaluronan

Naoki Itano*

Department of Molecular Oncology, Division of Molecular and Cellular Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency.

*To whom correspondence should be addressed to: Dr. Naoki Itano Department of Molecular Oncology, Division of Molecular and Cellular Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine; Nagano 390-8621, Japan, Tel: +81-263-37-2722, Fax: +81-263-37-2724. E-mail address: itano{at}sch.md.shinshu-u.ac.jp

Received January 23, 2008; Accepted February 13, 2008


  Abstract

Hyaluronan is a major macromolecular polysaccharide component of the extracellular matrix that confers structural frameworks for cells. Despite its relatively simple chemical composition, hyaluronan mediates many other important functional aspects including signaling activity during embryonic morphogenesis, cellular regeneration, and wound healing. Abnormalities in hyaluronan metabolism have been implicated in many diseases, such as inflammatory disorders, cardiovascular diseases, and cancer. To date, it has become increasingly clear that hyaluronan production in vertebrates is tightly regulated by three hyaluronan synthases and that hyaluronan catabolism is regulated by an enzymatic degradation reaction involving several hyaluronidases. Together, these discoveries have provided key insights into the physiological roles of hyaluronan and a deeper understanding of the mechanisms underlying altered hyaluronan turnover in diseases. The central aim of this review article is therefore to highlight the multiple roles of hyaluronan in physiological and pathological states via its complex turnover regulation.

Key Words: biosynthesis, cancer progression, cardiovascular disease, extracellular matrix, hyaluronan


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