Dermal Hyaluronan Is Rapidly Reduced by Topical Treatment with Glucocorticoids

Abstract

Skin atrophy is part of the normal ageing process, but is accelerated by topical glucocorticoid (GC) treatments that are widely used in dermatology. Hyaluronan (HA) is one of the most abundant components of the cutaneous extracellular matrix and is involved in tissue homeostasis, hydration, and repair processes, but little is known about the effects of GCs on HA synthesis and stability. Here we examined the regulation of HA metabolism in human skin during GC therapy. Expression of the HA synthesizing enzymes hyaluronan synthase (HAS)-2 and HAS-3 and the HA degrading enzymes HYAL-1, HYAL-2, and HYAL-3 in response to GC treatment was evaluated. HAS-2 expression was markedly suppressed by dexamethasone treatment of cultured fibroblasts and HaCaT keratinocyte cells, and in human skin biopsies taken from volunteers treated with dexamethasone ointment. Consistently, the HA content of cell culture supernatants and in human skin was reduced after dexamethasone treatment. Hyaluronidase expression and activity, on the other hand, was not altered by dexamethasone treatment. These data show that the levels of skin HA rapidly decrease after short-term GC treatment due to a reduction in HA synthesis, while HA degradation is not changed. This may reflect an initiation of skin atrophy in response to topically applied GCs.

Melanoma Cells Control HA Synthesis in Peritumoral Fibroblasts via PDGF-AA and PDGF-CC: Impact on Melanoma Cell Proliferation

“…These data are supported by comparative mRNA analyses of the HA-synthesizing enzyme HAS2, which is significantly stronger expressed in Fbs than in MM. In accordance with previous data (Gebhardt et al, 2010), the two other known HASs HAS1 and HAS3 are only expressed at low mRNA levels in both cell types. These findings suggest that the majority of tumor-promoting stromal HA originates from Fbs.…”

Identification and Molecular Analysis of Glycosaminoglycans in Cutaneous Lupus Erythematosus and Dermatomyositis

“…Interestingly, glucocorticoids can suppress HAS2 levels in cultured dermal fibroblasts (Zhang et al 2000;Gebhardt et al 2010), suggesting that one mechanism for their antiinflammatory effects may be the reduction of HA production. As for CS, the increase in CHSY1 and C4ST1 may be responsible for the accumulation of CS in CLE.…”

Regenerative potential of glycosaminoglycans for skin and bone

“…Furthermore, C4S and KS are common GAGs of the epidermis, whereas in the dermis, HA represents 75% of all GAGs [117]. Fibroblasts are the main source of dermal HA, and the HA-synthase 2 is their main constitutive synthesizing enzyme [118,119]. Besides being the source of HA, fibroblast physiology is also modulated by this GAG, mainly after binding to the HA receptor CD44 [44].…”