Hyaluronic acid in skin
The use of biotinylated HA-binding peptide91 revealed that not only cells of mesenchymal origin were capable of synthesizing HA and permitted the histolocalization of HA in the dermal compartment of skin and the epidermis.26,92-94 This technique enabled the visualization of HA in the epidermis, mainly in the ECM of the upper spinous and granular layers, whereas in the basal layer HA is predominantly intracellular.26
The function of the skin as a barrier is partly attributed to the lamellar bodies, thought to be modified lysosomes containing hydrolytic enzymes. They fuse with the plasma membranes of mature keratinocytes and they have the ability to acidify via proton pumps and partially convert their polar lipids into neutral lipids. Diffusion of aqueous material through the epidermis is blocked by these lipids synthesized by keratinocytes in the stratum granulosum. This boundary effect corresponds to the level of HA staining. The HA-rich area inferior to this layer may obtain water from the moisture-rich dermis, and the water contained therein cannot penetrate beyond the lipid-rich stratum granulosum. The hydration of the skin critically depends on the HA-bound water in the dermis and in the vital area of the epidermis, while maintenance of hydration essentially depends on the stratum granulosum. Extensive loss of the stratum granulosum in patients with burns may cause serious clinical problems due to dehydration.16
As mentioned above, skin HA accounts for most of 50% of total body HA.30 The HA content of the dermis is significantly higher than that of the epidermis, while papillary dermis has much greater levels of HA than reticular dermis.92 The HA of the dermis is in continuity with the lymphatic and vascular systems. HA in the dermis regulates water balance, osmotic pressure and ion flow and functions as a sieve, excluding certain molecules, enhancing the extracellular domain of cell surfaces and stabilizes skin structures by electrostatic interactions.16 Elevated levels of HA are synthesized during scar-free fetal tissue repair and the prolonged presence of HA assures such scar-free tissue repair.95-97 Dermal fibroblasts provide the synthetic machinery for dermal HA and should be the target for pharmacologic attempts to enhance skin hydration. Unfortunately, exogenous HA is cleared from the dermis and is rapidly degraded.