More than just a filler – the role of hyaluronan for skin homeostasis

Abstract

In recent years, hyaluronan (HA) has become an increasingly attractive substance as a non-immunogenic filler and scaffolding material in cosmetic dermatology. Despite its wide use for skin augmentation and rejuvenation, relatively little is known about the molecular structures and interacting proteins of HA in normal and diseased skin. However, a comprehensive understanding of cutaneous HA homeostasis is required for future the development of HA-based applications for skin regeneration.This review provides an update on HA-based structures, expression, metabolism and its regulation, function and pharmacological targeting of HA in skin.

Glycosaminoglycan and proteoglycan in skin aging

“…Except HA, GAGs are generally heavily glycosylated on their related proteoglycan (PG) core proteins ( Table 1) [7][8][9][10][11][12], and synthesized by various glycosyltransferases and sulfotransferases (Supplementary Table S1) [10][11][12][13]. In contrast, HA is synthesized as a single polysaccharide chain without a core protein partner and non-covalently binds to many proteins containing HA-binding domain [13,14]. Because GAG chains contain numerous negatively charged carboxyl and sulfate groups, they may have important roles in maintaining water in tissue [6].…”

“…Because GAG chains contain numerous negatively charged carboxyl and sulfate groups, they may have important roles in maintaining water in tissue [6]. In particular, HA was reported to be able to hold water molecules up to 1000-fold of its molecular weight [14].…”

“…HA is a linear nonsulfated GAG composed of up to 10,000 repeats of its disaccharide unit D-glucuronic acid (ß13) and N-acetyl-D-glucosamine (ß14) [14]. HA synthesis occurs in the plasma membrane by three HA synthases (HAS1-3), and the synthesized HA molecules are directly secreted out of the cell membrane [14]. HAS1 and HAS2 are reported to produce 2-4  10 6 Da of HA, while HAS3 produces 0.4-2.5  10 5 Da of HA [14].…”

“…HA synthesis occurs in the plasma membrane by three HA synthases (HAS1-3), and the synthesized HA molecules are directly secreted out of the cell membrane [14]. HAS1 and HAS2 are reported to produce 2-4  10 6 Da of HA, while HAS3 produces 0.4-2.5  10 5 Da of HA [14]. HAS2 is thought to be the main synthase in the skin [14].…”

Influence of the Macro- and/or Microstructure of Cross-Linked Hyaluronic Acid Hydrogels on the Release of Two Model Drugs

“…HA is distributed throughout the human body and occurs in almost all biological tissues and fluids [1,2]. Due to its unique properties, including full biodegradability, biocompatibility, nontoxicity, high water absorption capacity, and nonimmunogenicity [3,4], this biopolymer is widely used for many medical applications.…”