Fifty-kDa Hyaluronic Acid Upregulates Some Epidermal Genes without Changing TNF-α Expression in Reconstituted Epidermis

Background: Due to its strong water binding potential, hyaluronic
acid (HA) is a well-known active ingredient for cosmetic
applications. However, based on its varying molecular size, skin
penetration of HA may be limited. Recent studies have demonstrated
that low-molecular-weight HA (LMW HA) may show a certain
proinflammatory activity. We thus aimed to characterize an
LMW-sized HA molecule that combines strong anti-aging abilities
with efficient skin penetration but lacks potential proinflammatory
effects. Methods: Total RNA and total protein were isolated from
reconstituted human epidermis following incubation with HAs of
various molecular weights (20, 50, 130, 300, 800 and 1,500 kDa).
Tumor necrosis factor-alpha expression was determined using
quantitative PCR. Genonnic and proteomic expression of various
junctional proteins was determined using Affymetrix and common
Western blotting techniques. Results: LMW HA of approximately 50
kDa did not significantly alter tumor necrosis factor-alpha
expression compared to 20-kDa HA, but revealed significantly higher
skin penetration rates than larger sized HA associated with
increased expression of genes and proteins known to be involved in
tight junction formation and keratinocyte cohesion. Conclusion: LMW
HA of approximately 50 kDa shows better penetration abilities than
larger-sized HA. In addition, LMW HA influences the expression of
various genes including those contributing to keratinocyte
differentiation and formation of intercellular tight junction
complexes without showing proinflammatory activity. These
observations contribute to current knowledge on the effects of LMW
HA on keratinocyte biology and cutaneous physiology. Copyright (C)
2011 S. Karger AG, Basel