Epidermal Hyaluronan in Barrier Alteration-Related Disease

Abstract

In skin, although the extracellular matrix (ECM) is highly developed in dermis and hypodermis, discrete intercellular spaces between cells of the living epidermal layers are also filled with ECM components. Herein, we review knowledge about structure, localization and role of epidermal hyaluronan (HA), a key ECM molecule. HA is a non-sulfated glycosaminoglycan non-covalently bound to proteins or lipids. Components of the basal lamina maintain some segregation between the epidermis and the underlying dermis, and all epidermal HA is locally synthesized and degraded. Functions of HA in keratinocyte proliferation and differentiation are still controversial. However, through interactions with partners, such as the TSG-6 protein, HA is involved in the formation, organization and stabilization of the epidermal ECM. In addition, epidermal HA is involved in the formation of an efficient epidermal barrier made of cornified keratinocytes. In atopic dermatitis (AD) with profuse alterations of the epidermal barrier, HA is produced in larger amounts by keratinocytes than in normal skin. Epidermal HA inside AD lesional skin is located in enlarged intercellular spaces, likely as the result of disease-related modifications of HA metabolism.

Hyaluronic Acid Hydrogel Containing Resveratrol-Loaded Chitosan Nanoparticles as an Adjuvant in Atopic Dermatitis Treatment

“…Several studies reported that HA-based transdermal delivery systems exhibit excellent biocompatibility, enhanced permeability, and efficient localized release of topical anti-inflammatory drugs, inhibiting eczema-associated skin inflammation [ 39 ]. Moreover, the bioactive effect of hyaluronic acid in filling the intercellular spaces of the living epidermal layers is well known, highlighting its role in the treatment of AD pathology [ 40 ]. These properties, alongside the enhanced controlled release abilities, improved targeting capacity to the skin strata, and easy manipulation of swelling level [ 41 ], make HA gels efficient devices for topical drug delivery.…”

Effects on keratinocytes of the traditional combination of herb extract (Royal Oji Complex) implicated the improvement of young children's skin moisture and barrier

“…Among these isoenzymes, HAS3 is very active and is responsible for synthesizing low molecular weight polymers; there is significant mRNA expression of HAS3 in healthy keratinocytes. 16,17 Epidermal ceramides, mainly accounted for by acyl-ceramides, are crucial for skin barrier function. They are secreted from stratum granulosum cells to form a part of the cornified envelope and create sheets of lipid lamellae, resulting in an impenetrable barrier in the SC.…”

Synergy of GHK‐Cu and hyaluronic acid on collagen IV upregulation via fibroblast and ex‐vivo skin tests

“…LMW HA (MW < 10 K Da) was found to stimulate the migration and proliferation of endothelial cells, promote the synthesis of collagen, 15 and upregulate inflammatory mediators. While, HMW HA (MW > 1000 K Da) was reported to inhibit the production of pro‐inflammatory mediators, 16‐19 decrease oxidative stress, and inhibit angiogenesis 20‐22 . In addition, chemically modified HA, such as acetylated HA (AcHA), shows better bioavailability than normal HA, 23 being able to decrease MMP expression and slow down ECM degradation induced by chronobiological and extrinsic aging 24 …”

“…While, HMW HA (MW > 1000 K Da) was reported to inhibit the production of pro-inflammatory mediators, [16][17][18][19] decrease oxidative stress, and inhibit angiogenesis. [20][21][22] In addition, chemically modified HA, such as acetylated HA (AcHA), shows better bioavailability than normal HA, 23 being able to decrease MMP expression and slow down ECM degradation induced by chronobiological and extrinsic aging. 24 However, the co-effect of GHK-Cu and HA was rarely reported.…”