Paeonol에 의한 표피줄기세포 활성화 = Activating the Proliferation of Keratinocyte Stem Cells by Paeonol, a Compound from Natural Herb

국문 초록 (Abstract)

피부의 가장자리에 위치한 표피는 개체의 생존에 절대적으로 중요하며, 기저막에 위치한 표피줄기세포에 의해 평생 끊임없이 재생되고 있다. 표피줄기세포는 한정된 세포분열을 진행하고 각질세포로 분화하는 transit amplifying (TA)세포를 만들어 냄으로써 오랜 기간 재생에 필요한 많은 각질세포를 만들어 낼 수 있다. 본 연구에서는 표피줄기세포 세포분열 활성화 화합물로 목단으로부터 추출한 페오놀(paeonol)을 350여 개의 화합물들로부터 검색해 냈다. 이러한 세포분열 활성화 효능은 표피줄기세포 특이적으로 나타나며, 표피줄기세포의 지표로 알려진 p63 단백질의 발현 경향은 페오놀을 처리한 표피줄기세포에서 변화하지 않음을 유세포분석법으로 확인하였다. 콜로니형성 분석에서는 페오놀을 처리한 표피줄기세포가 1.3배 이상 더 나은 콜로니 형성능을 보여주었다. 그리고 PCR array 분석을 통해서 페오놀의 효능은 여러 신호전달에 의해 나타남을 알 수 있었다. 이러한 결과들로부터 페오놀이 줄기세포성에 영향을 주지 않고 표피줄기세포의 재생능력을 향상시키므로 표피줄기 세포 활성화 물질로서 화장품 소재로 적용될 수 있을 것으로 판단된다.

다국어 초록 (Multilingual Abstract)

Epidermis is continuously regenerated by keratinocyte stem cells (KSCs) residing in basement membrane, which is critical to the survival of an organism. KSCs are believed to persist during the whole lifetime and generate an enormous number of keratinocytes, required for the maintenance of epidermis, through transit amplifying cells dividing definite times until they become differentiated. In this report, we have developed a phenolic compound, paeonol, purified from Moutan Cortex, as a KSC proliferation activator, by screening about 350 herbal compounds. The cell proliferation activation by paeonol is specific for KSC not for keratinocyte, and no significant difference in the expression of p63 protein, a KSC marker, in KSCs treated with paeonol was observed in FACS analysis with anti-p63 antibody. In the colony forming assay, paeonol-treated KSC showed improved colony forming activity more than 1.3 fold. In addition, the result of PCR array shows that the activity of paeonol is through several signal pathways involving stem cell functions. These results suggest that paeonol could enhance KSC proliferation activity without reduction in stemness and could be applied to cosmetics as a KSC activating ingredient.

참고문헌 (Reference)

1 M. Senoo, "p63is essential for the proliferative potential of stem cells in stratified epithelia" 129 (129): 523-, 2007

2 G. Pellegrini, "p63 identifies keratinocyte stem cells" 98 (98): 3156-, 2001

3 X. Su, "TAp63 prevents premature aging by promoting adult stem cell maintenance" 5 (5): 64-, 2009

4 L. Alonso, "Stem cells of the skin epithelium" 100 (100): 11830-, 2003

5 H. R. Choi, "Oligosaccharides of hyaluronic acid increased epidermal cell stemness by modulation of integrin expression" 11 (11): 290-, 2012

6 A. Webb, "Location and phenotype of human adult keratinocyte stem cells of the skin" 72 (72): 387-, 2004

7 P. Kaur, "Interfollicular epidermal stem cells: identification, challenges, potential" 126 (126): 1450-, 2006

8 R. M. Lavker, "Epidermal stem cells:properties, markers, and location" 97 (97): 13473-, 2000

9 C. Blanpain, "Epidermal stem cells of the skin" 22 : 339-, 2006

10 J. R. Bickenbach, "Epidermal stem cells have the potential to assist in healing damaged tissues" 11 (11): 118-, 2006

11 N. Gago, "Age-dependent depletion of human skin-derived progenitor cells" 27 (27): 1164-, 2009