A Connecting Link between Hyaluronan Synthase 3-Mediated Hyaluronan Production and Epidermal Function

Area of Science:

• Dermatology
• Biochemistry
• Extracellular Matrix Research

Background:

• Hyaluronan (HA) is a key skin extracellular matrix component synthesized by HA synthases (HAS1-3).
• Epidermal HA's role in cell proliferation and differentiation is debated, with some studies showing no effect upon HA depletion.

Purpose of the Study:

• To investigate the specific roles of epidermal HA and HAS3 in regulating epidermal turnover and architecture.
• To compare the effects of HA depletion using Streptomyces hyaluronidase (St-HAase), 4-methylumbelliferone (4MU), and HAS3 knockdown via siRNA.

Main Methods:

• Utilized reconstructed human epidermis (epidermal equivalents).
• Employed siRNA-mediated knockdown of HAS3.
• Applied St-HAase and 4MU for HA depletion.
• Assessed epidermal architecture, turnover, HA content, keratinocyte proliferation, and differentiation.

Main Results:

• St-HAase treatment did not significantly alter epidermal architecture or turnover.
• 4MU treatment reduced keratinocyte proliferation and epidermal thickness but had minimal impact on extracellular HA levels.
• siRNA-mediated knockdown of HAS3 significantly decreased epidermal HA content and thickness, alongside reduced keratinocyte proliferation and differentiation.

Conclusions:

• HAS3-mediated HA production plays a crucial role in keratinocyte proliferation and differentiation in developing epidermis.
• Extracellularly deposited HA may have a less significant role compared to HAS3-dependent HA production in epidermal development.