Hyaluronan participates in the epidermal response to disruption of the permeability barrier in vivo.
Hyaluronan (hyaluronic acid, HA) is a glycosaminoglycan in the extracellular matrix of tissues that plays a role in cellular migration, proliferation and differentiation. Injury to the stratum corneum elicits an epidermal hyperproliferative response, a pathogenic feature in many cutaneous diseases including eczema and psoriasis. Because HA is abundant in the matrix between keratinocytes, we asked whether the presence of HA is required for epidermal hyperplasia to occur in response to barrier injury. Disruption of the stratum corneum, by acetone application on the skin of hairless mice, led to a marked accumulation of HA in the matrix between epidermal basal and spinous keratinocytes, and also within keratinocytes of the upper epidermis. To test whether HA may have a functional role in epidermal hyperplasia, we used Streptomyces hyaluronidase (StrepH), delivered topically, to degrade epidermal HA and blunt the accumulation of epidermal HA after acetone. StrepH signficantly reduced epidermal HA levels, and also significantly inhibited the development of epidermal hyperplasia. This reduction in epidermal thickness was not attributable to any decrease in keratinocyte proliferation, but rather to an apparent acceleration in terminal differentiation (ie, increased keratin 10 and filaggrin expression). Overall, the data show that HA is a significant participant in the epidermal response to barrier injury.
Biomedical Engineering, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. maytine@ccf.org.
Edward V
EV
Maytin
Helen H
HH
Chung
V Mani
VM
Seetharaman
D000096:Acetone / Q000494:pharmacology; D000818:Animals; D004817:Epidermis / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D006965:Hyperplasia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D018613:Microscopy, Confocal; D010539:Permeability / Q000187:drug effects; D012997:Solvents / Q000494:pharmacology
D012997:Solvents; D000096:Acetone; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase