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

Soyun Cho^*^,^,^,**, Hyeon Ho Kim^*^,^,, Min Jung Lee^*^,^,, Serah Lee^*^,^,, Chang-Seo Park, Sang-June Nam, Jeong-Jun Han, Jin-Wook Kim and Jin Ho Chung¹^,*^,^,

^* Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea
Laboratory of Cutaneous Aging Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
Institute of Dermatological Science, Seoul, Korea
^** Boramae Hospital, Seoul National University, Seoul, Korea
Department of Chemical and Biochemical Engineering, Dongguk University, Seoul, Korea
Doosan Biotech Division, Gyeonggido, Korea

This work was supported in part by Grant A040008 from the KoreaHealth 21 R & D Project, Ministry of Health and Welfare,Republic of Korea.

Published, JLR Papers in Press, March 12, 2008.

^¹ To whom correspondence should be addressed. e-mail: jhchung{at}snu.ac.kr

In an effort to find topical agents that prevent or retard cutaneousaging, seven functional lipids were screened for their procollagen-upregulatingand matrix metalloproteinase (MMP)-1-downregulating activitiesin human dermal fibroblasts by Western blotting. The preventiveeffect on ultraviolet (UV)-induced decrease of procollagen wasdemonstrated 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 unirradiatedbasal conditions. The inhibitory effect on UV-induced MMP-1expression was seen in NAPS, TAPS, LPA, PS, lysophosphatidylglycerol,and LPS. PS was chosen as the most suitable candidate anti-agingchemical for the subsequent in vivo studies. We investigatedthe effects of PS on acute UV response and chronologic skinaging by topically applying it to young skin before UV irradiationand to aged human skin, respectively. Real-time PCR and Westernblot revealed that in the young skin, PS treatment preventedUV-induced reduction in procollagen expression and inhibitedUV-induced MMP-1 expression. PS also blocked UV-induced IL-6and COX-2 gene expression in cultured fibroblasts dose-dependently.In the aged skin, PS caused increased procollagen transcriptionand procollagen immunostaining in the upper dermis, and a significantdecrease in MMP-1 expression at both mRNA and protein levels.These results indicate that topical PS has anti-skin-aging propertiesand point to the potential use of PS as a therapeutic agentin the prevention and treatment of cutaneous aging.

Supplementary key words ultraviolet • intrinsic aging • photoaging • matrix metalloproteinase-1

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