Q

Dermal Hyaluronan

The HA content of the dermis is far greater than that of the epidermis, and accounts for most of the 50% of total body HA present in skin. The papillary dermis has the more prominent levels of HA than does reticular dermis (96). The HA of the dermis is in continuity with both the lymphatic and vascular systems, which epidermal HA is not. Exogenous HA is cleared from the dermis and rapidly degraded.

The dermal fibroblast provides the synthetic machinery for dermal HA, and should be the target for pharmacological attempts to enhance skin hydration. The fibroblasts of the body, the most banal of cells from a histological perspective, is probably the most diverse or all vertebrate cells with the broadest repertoire of biochemical reactions and potential pathways for differentiation. Much of this diversity is site-specific. What makes the papillary dermal fibroblast different from other fibroblasts is not known. However, these cells have an HA synthetic capacity similar to that of the fibroblasts that line the joint synovium responsible for the HA-rich synovial fluid (Stern, unpublished experiments).

Aging Skin

Though dermal HA is responsible for most skin HA, epidermal cells are also able to synthesize HA. The most dramatic histochemical change observed in senescent skin is the marked decrease in epidermal HA (96). In senile skin, HA is still present in the dermis, while the HA of the epidermis has disappeared entirely. The proportion of total GAG synthesis devoted to HA is greater in epidermis that in dermis, and the reasons for the precipitous fall with aging is unknown. The synthesis of epidermal HA is influenced both by the underlying dermis, as well as by topical treatments, such as with retinoic acids, indicating that epidermal HA is under separate controls from dermal HA.

In contrast with previous in vitro (124,125) and in vivo (126,127) observations, recent studies document that the total level of HA remains constant in the dermis with aging. The major age-related change is the increasing avidity of HA with tissue structures with the concomitant loss of HA extractability. Such intercolated HA may have diminished ability to take on water of hydration. This decreased volume of water of hydration HA is obviously a loss in skin moisture. An important study for the future would be to define precisely the hyaladherins, the HA-binding proteins, that decorate the HA in senile skin, and to compare that profile with the hyaladherins of young skin, in both the dermal and epidermal compartments. Progressive loss in the size of the HA polymer in skin as a function of age has also been reported (128).

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