Hyaluronic Acid and Dermatan Sulfate Are Selectively Stimulated by Retinoic Acid in Irradiated and Nonirradiated Hairless Mouse Skin

Abstract

All-trans retinoic acid (RA) has been shown to enhance subepidermal repair in photoaged hairless mice. The current study assesses the effects of RA on the glycosaminoglycan (GAG) content in irradiated and nonirradiated mouse skin. Mice were exposed to ultraviolet B (UVB) for 10 wk, after which they were treated either with 0.05% RA or with an ethanolpolyethylene glycol 400 vehicle three times a week for 10 or 20 wk. When assessed at the end of 10 wk of UVB irradiation, the GAG content had doubled, without a change in the hyaluronic acid (HA) to dermatan sulfate (DS) ratio. When irradiation was discontinued, the GAG content decreased progressively until the end of the experimental period. This decline was totally inhibited by RA treatment and could be ascribed to a marked increase in hyaluronic acid (78%), whereas no significant change in DS was observed. In nonirradiated skin, however, topical RA increased GAG levels mainly by a pronounced increase in the content (50%) and the synthesis (40%) of DS. In untreated mice, the HA/DS ratio decreased significantly with age in both irradiated and nonirradiated mice. Interestingly, RA maintained this ratio only in animals exposed to UVB. In addition, there was a marked stimulation in the heparin content, up to approximately 20-fold, after irradiation, whereas the amount of heparin in both irradiated and nonirradiated skin increased about 2- to 3-fold with RA treatment. In summary, the alterations induced in HA and DS contents in irradiated and nonirradiated skin indicate the specificity of the RA-induced effects for the various GAGs.

Chronic Ultraviolet B Irradiation Causes Loss of Hyaluronic Acid from Mouse Dermis Because of Down-Regulation of Hyaluronic Acid Synthases

“…Interestingly, several conditions that accelerate skin aging such as estrogen deficiency 13,14 are associated with loss of HA from the dermis, and treatments that counteract actinic skin aging such as retinoic acid increase dermal HA. 15,16 These results strongly suggest that dermal HA plays an important role during photoaging.…”

“…Some studies reported increased HA content in UV-irradiated skin of mice, 39,40 whereas others reported reduced HA content. 16,41 The contradictory results of these studies might be attributable to the fact that different irradiation protocols were used that varied in dose and duration of the UV exposure and the time of analysis. It is likely that the acute effect of UV irradiation on dermal HA is different from the longterm effects of chronic UV irradiation.…”

“…This is in line with another study in mice showing progressive loss of HA even after cessation of UVB irradiation. 16 The progressive long-term down-regulation of all HAS isoenzymes after the end of the UVB irradiation protocol suggests that UVB does not inhibit HAS expression directly. This conclusion was supported by the present in vitro result that acute UVB irradiation induces rather than inhibits HAS1 and HAS3 expression.…”

The decreased secretion of hyaluronan by older human fibroblasts under physiological conditions is mainly associated with the down-regulated expression of hyaluronan synthases but not with the expression levels of hyaluronidases

“…In photoShuko Terazawa and Hiroaki Nakajima have contributed equally to this work. aged skin, there is a marked deficiency of HA (Margelin et al 1996;Takahashi et al 1995Takahashi et al , 1996 in addition to the fragmentation and loss of type I collagen fibrils due to the up-regulated activity of matrix-metalloproteinase (MMP)-1 (Fisher et al 2008(Fisher et al , 2009). Available evidence indicates that naturally aged, sun-protected skin and photoaged skin share important molecular features, including connective tissue damage, elevated matrix metalloproteinase levels and reduced collagen production (Varani et al 2001(Varani et al , 2002.…”

Análise mecânica e histológica do tegumento facial com seqüela de queimadura após tratamento tópico com tretinoína

“…Diferentes elementos da matriz são seletivamente estimulados ou modulados. O estímulo ao TGF-β, indiretamente, estimula a expressão gênica de vários componentes da matriz extracelular 49 .…”