대한화장품학회지 (Journal of the Society of Cosmetic Scientists of Korea)

  • 제47권3호
  • /
  • Pages.205-212
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  • 2021
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  • 1226-2587(pISSN)
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  • 2288-9507(eISSN)
대한화장품학회 (Society of Cosmetic Scientists of Korea)
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섬유아세포에서 프로모터 다형성에 의한 Matrix Metalloproteinase-1의 발현에 관한 연구

Study on the Expression of Matrix Metalloproteinase-1 by Promoter Polymorphism in Human Dermal Fibroblast

  • 이진우 (한국과학기술연구원 천연물연구소) ;
  • 정유정 (한국과학기술연구원 천연물연구소) ;
  • 봉심규 (한국과학기술연구원 천연물연구소) ;
  • 박노준 (한국과학기술연구원 천연물연구소) ;
  • 이상헌 (한국과학기술연구원 천연물연구소) ;
  • 노민수 (서울대학교 약학대학) ;
  • 임경민 (이화여자대학교 약학대학) ;
  • 김수남 (한국과학기술연구원 천연물연구소)
  • Lee, Jin Woo (Natural Products Research Institute, Korea Institute of Science and Technology) ;
  • Jung, Yujung (Natural Products Research Institute, Korea Institute of Science and Technology) ;
  • Bong, Sim-Kyu (Natural Products Research Institute, Korea Institute of Science and Technology) ;
  • Park, No-June (Natural Products Research Institute, Korea Institute of Science and Technology) ;
  • Lee, Sang Heon (Natural Products Research Institute, Korea Institute of Science and Technology) ;
  • Noh, Minsoo (College of Pharmacy, Seoul National University) ;
  • Lim, Kyung-Min (College of Pharmacy, Ewha Womans University) ;
  • Kim, Su-Nam (Natural Products Research Institute, Korea Institute of Science and Technology)
  • 투고 : 2021.07.28
  • 심사 : 2021.09.10
  • 발행 : 2021.09.30
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초록

본 연구는 피부 섬유아세포에 자외선을 조사하거나 TNF-α를 처리하면 세포에 따라 MMP-1의 발현이 다르게 나타나는데, 이것이 MMP-1 프로모터의 다형성에 의해서 나타남을 밝히기 위해 수행되었다. 시판하는 23 종의 primary 섬유아세포에 대하여 MMP-1 프로모터의 -1607 부위의 유전형을 분석한 결과 6 개의 1G/1G 유전형, 10 개의 1G/2G 유전형, 7 개의 2G/2G 유전형을 가진 섬유아세포를 확인할 수 있었다. Hs68과 Detroit 551 세포주는 1G/2G 유전형을 가지는 것으로 확인되었다. 1G/1G 유전형은 TNF-α 처리에 의해 대조군에 비해 MMP-1이 2 배 높게 발현되었으며, 자외선에 의해서는 거의 발현되지 않았다. 1G/2G 유전형의 경우는 TNF-α 처리에 의해 MMP-1이 2.45 배 높게 발현되었으며, 자외선에 의해서는 1.4 배 MMP-1이 발현되었다. 2G/2G 유전형의 경우는 TNF-α 처리에 의해 MMP-1이 1.35 배 발현되었으며, 자외선에 의해서는 2.5 배로 높게 발현되었다. 즉 1G 유전형은 TNF-α에 의해, 2G 유전형은 자외선에 의해 발현이 유도되는 것으로 추정할 수 있으며, -1607 위치에 하나 더 삽입된 G에 의해서 Ets 전사인자가 결합할 수 있는 site가 만들어져서 MMP-1의 발현이 증가한다고 추정할 수 있으며, 피부 노화와 관련하여 섬유아세포에서는 이에 대한 연구가 전혀 진행되어 있지 않아서 향후 추가로 연구되어야 할 부분이다. 피부는 내인성 노화와 광노화의 영향을 동시에 받는 기관이므로, 피부 노화를 개선하기 위한 타겟으로 MMP-1의 발현을 분석할 경우에는 실험 조건에 적합한 유전형을 가지는 세포를 선택하여 연구를 진행하는 전략을 세워야 할 필요성이 대두된다.

The skin fibroblasts of different origins showed different expression levels of MMP-1 in response to TNF-α treatment or UV irradiation. We hypothesized that this is caused by polymorphism in the MMP-1 promoter region. To elucidate it, first of all, we analyzed and classified the genotype of the -1607 site of the MMP-1 promoter in 23 commercially available primary fibroblasts, and then we examined the expression of MMP-1 by TNF-α or UVB stimulation for each classified genotype. As a result of the analysis, fibroblasts with 6 1G/1G genotypes, 10 1G/2G genotypes, and 7 2G/2G genotypes were identified. Hs68 and Detroit 551 cell lines were confirmed to have 1G/2G genotypes. In the 1G/1G genotype, MMP-1 was expressed twice as high as that of the control group by TNF-α treatment, and was hardly expressed by UV light. In the case of the 1G/2G genotype, MMP-1 was expressed 2.45 fold higher by TNF-α treatment, and 1.4 fold by UV light than the control. In the case of the 2G/2G genotype, MMP-1 was expressed 1.35 fold by TNF-α treatment, and was highly expressed by 2.5 fold by ultraviolet rays compared to control. It can be estimated that MMP-1 expression is better induced in the 1G genotype by TNF-α and in the 2G genotype by UV light. In addition, it can be presumed that MMP-1 expression is increased by creating a site where the Ets transcription factor can bind by another G inserted at the -1607 position. These studies have not been conducted at all in fibroblasts in relation to skin aging, so it is an area that needs to be further studied in the future. In conclusion, since the skin is an organ that is affected by both intrinsic aging and photoaging at the same time, when analyzing the expression of MMP-1 as a target for improving skin aging, it is necessary to select cells with a genotype suitable for the experimental conditions of the study.

키워드

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