Hyaluronan Participates in the Epidermal Response to Disruption of the Permeability Barrier in Vivo

Abstract

Hyaluronan (hyaluronic acid, HA) is a glycosaminoglycan in the extracellular matrix of tissues that plays a role in cellular migration, proliferation and differentiation. Injury to the stratum corneum elicits an epidermal hyperproliferative response, a pathogenic feature in many cutaneous diseases including eczema and psoriasis. Because HA is abundant in the matrix between keratinocytes, we asked whether the presence of HA is required for epidermal hyperplasia to occur in response to barrier injury. Disruption of the stratum corneum, by acetone application on the skin of hairless mice, led to a marked accumulation of HA in the matrix between epidermal basal and spinous keratinocytes, and also within keratinocytes of the upper epidermis. To test whether HA may have a functional role in epidermal hyperplasia, we used Streptomyces hyaluronidase (StrepH), delivered topically, to degrade epidermal HA and blunt the accumulation of epidermal HA after acetone. StrepH signficantly reduced epidermal HA levels, and also significantly inhibited the development of epidermal hyperplasia. This reduction in epidermal thickness was not attributable to any decrease in keratinocyte proliferation, but rather to an apparent acceleration in terminal differentiation (ie, increased keratin 10 and filaggrin expression). Overall, the data show that HA is a significant participant in the epidermal response to barrier injury. Hyaluronan (hyaluronic acid, HA) is a large glycosaminoglycan (carbohydrate polymer) that is abundant in many tissues, where it acts as a hydrating agent and an organizer of proteins that form structural scaffolding in tissues such as cartilage and dermis.

Hoxb13 Up-regulates Transglutaminase Activity and Drives Terminal Differentiation in an Epidermal Organotypic Model

“…(ii) In mouse cutaneous wounds, Hoxb13 epidermal expression is up-regulated at a time when epidermal proliferation is down-regulated and terminal differentiation is up-regulated (24). (iii) HA, which has been shown to inhibit differentiation in REK cultures (25) and is also thought to inhibit differentiation in vivo (47), is significantly reduced in the basal layer of Hoxb13-overexpressing REK lift tissue. Parenthetically, cells undergoing stress produce high levels of HA (30).…”

Low Dose Ultraviolet B Irradiation Increases Hyaluronan Synthesis in Epidermal Keratinocytes via Sequential Induction of Hyaluronan Synthases Has1–3 Mediated by p38 and Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII) Signaling*

“…Similarly, Has3 can be induced by proinflammatory cytokines in synovial membrane cells (88). This kind of acute increase in epidermal hyaluronan can be considered as an adaptive response to restore homeostasis, much like those seen after wounding (22) and epidermal barrier disruption (89).…”

Lamellar Bodies of Human Epidermis

“…Nothing is known about the secretion of extracellular matrix elements in the stratum granulosum, although the extracellular matrix is increasingly being considered as important for the properties and function of the stratum corneum (59). This identification leads us to suppose that LBs may be involved in the secretion of extracellular matrix components in the upper epidermis.…”