Phosphatidylserine prevents UV-induced decrease of type I procollagen and increase of MMP-1 in dermal fibroblasts and human skin in vivo

Abstract

In an effort to find topical agents that prevent or retard cutaneous aging, seven functional lipids were screened for their procollagen-upregulating and matrix metalloproteinase (MMP)-1-downregulating activities in human dermal fibroblasts by Western blotting. The preventive effect on ultraviolet (UV)-induced decrease of procollagen was demonstrated in phosphatidylserine (PS), lysophosphatidylserine (LPS), lysophosphatidic acid (LPA), N-acetyl phytosphingosine (NAPS), and tetraacetyl phytosphingosine (TAPS). Furthermore, PS, LPS, and LPA upregulated procollagen expression in unirradiated basal conditions. The inhibitory effect on UV-induced MMP-1 expression was seen in NAPS, TAPS, LPA, PS, lysophosphatidylglycerol, and LPS. PS was chosen as the most suitable candidate anti-aging chemical for the subsequent in vivo studies. We investigated the effects of PS on acute UV response and chronologic skin aging by topically applying it to young skin before UV irradiation and to aged human skin, respectively. Real-time PCR and Western blot revealed that in the young skin, PS treatment prevented UV-induced reduction in procollagen expression and inhibited UVinduced MMP-1 expression. PS also blocked UV-induced IL-6 and COX-2 gene expression in cultured fibroblasts dosedependently. In the aged skin, PS caused increased procollagen transcription and procollagen immunostaining in the upper dermis, and a significant decrease in MMP-1 expression at both mRNA and protein levels.These results indicate that topical PS has anti-skin-aging properties and point to the potential use of PS as a therapeutic agent in the prevention and treatment of cutaneous aging. Skin aging is the sum of intrinsic aging and photoaging caused by repeated exposure to ultraviolet (UV) light. Whereas naturally aged skin is smooth, pale, and finely wrinkled, photoaged skin shows coarse, deep wrinkles and dyspigmentation and telangiectasia (1). In both chronologic aging and photoaging, decreased procollagen expression and increased matrix metalloproteinases (MMPs), a group of matrix-degrading enzymes secreted by epidermal keratinocytes and dermal fibroblasts, are characteristic. The alterations in collagen, the major structural component of the dermis, are thought to be responsible for wrinkle formation (2).MMP expression is increased by various stimuli, including UV light, oxidative stress, and cytokines. UV irradiation induces MMPs, including MMP-1 (collagenase), , and MMP-9 (gelatinase) (3). UVinduced MMP-1 initiates collagen breakdown by cleaving the fibrillar collagen (types I and III) at a single cleavage site. Once collagen is cleaved by MMP-1, it is further degraded by MMP-3 and MMP-9, whose expression levels are also increased by UV irradiation (3).The search for topical agents that prevent or retard cutaneous aging has become the quest of many basic researchers as well as the pharmaceutical and cosmeceutical industries. As part of the endeavor, in this study, seven functional lipids, including two sphingolipids and five phospholipids, were...

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