Role of hyaluronan in epithelial regeneration and wound healing

Investigators: Drs. Monslow, Mack, Ajani, Maytin

Collaborator: Dr. V. Hascall

Ha schematic

Figure 1. The disaccharide subunit of HA comprises one glucuronic acid and one N-acetylglucosamine molecule. The huge HA polymer, made up of this subunit repeated thousands of times, can be as large as 4 megadaltons in size. From: http://www.glycoforum.gr.jp/science/hyaluronan/HA01/HA01E.html

Hyaluronic acid (hyaluronan, or HA) is an abundant molecule in the extracellular space between keratinocytes. After wounding of skin, the level of HA within the skin accumulates dramatically (Fig. 2). Our data indicate that HA regulates the rate of epidermal proliferation and differentiation, both during normal homeostasis in the skin as well as after cutaneous injury. Our experiments with a bioengineered epidermal model, and in the skin of living mice, have demonstrated that HA has a functional role in differentiation of keratinocytes both in normal homeostasis and in response to injury.

REK model

Figure 2. A schematic diagram to show the epidermal differentiation program . HA between the epithelial cells is shown in yellow.

HA in mouse skin

Figure 3. Levels of epidermal HA are increased following incisional wounding of mouse skin. Scalpel was at location with (*). Yellow signal represents binding of HA-binding probe. Note that the intensity of HA in the epidermis (above dotted line) increases dramatically at 3 days. Ref: Maytin et al 2003.

References:

Maytin EV, Chung HH, Seetharaman VM. Hyaluronan participates in the epidermal response to disruption of the permeability barrier in vivo. Am J Pathol 2004; 165:1331-1341.

Passi A, Sadeghi P, Kawamura H, Anand S, Sato N, White LE, Hascall VC, Maytin EV. Hyaluronan suppresses late markers of epidermal differentiation in organotypic cultures of rat keratinocytes. Exper Cell Res. 2004; 296:123-134.

Maytin EV, Mack JA, Sato N, Anand S, Chung HH. Upregulation of hyaluronan in the epidermis during cutaneous wound healing in vitro and in vivo. In: Balazs E, Hascall V, editors. Proceedings of Hyaluronan 2003, An international conference, Cleveland, Ohio Oct 11-16, 2003. 15 pages. Matrix Biology Institute. Published online at: http://www.matrixbiologyinstitute.org/ha03/toc.htm