Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Regulation of Matrix Metalloproteinase-1 Expression by the Homeodomain Transcription Factor Caudal in Drosophila Intestine

초파리 장조직에서 Caudal 전사조절인자에 의한 matrix metalloproteinase-1 발현 조절

  • Lee, Shin-Hae (Department of Molecular Biology, Colleges of Natural Sciences, Pusan National University) ;
  • Hwang, Mi-Sun (Department of Molecular Biology, Colleges of Natural Sciences, Pusan National University) ;
  • Choi, Yoon-Jeong (Department of Molecular Biology, Colleges of Natural Sciences, Pusan National University) ;
  • Kim, Young-Shin (Research Institute of Genetic Engineering, Pusan National University) ;
  • Yoo, Mi-Ae (Department of Molecular Biology, Colleges of Natural Sciences, Pusan National University)
  • 이신해 (분자생물학과 부산대학교) ;
  • 황미선 (분자생물학과 부산대학교) ;
  • 최윤정 (분자생물학과 부산대학교) ;
  • 김영신 (유전공학연구소 부산대학교) ;
  • 유미애 (분자생물학과 부산대학교)
  • Received : 2012.10.30
  • Accepted : 2012.12.11
  • Published : 2012.12.30
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Abstract

The matrix metalloproteinase (MMP) family plays essential roles in physiological processes such as embryonic development, angiogenesis, wound healing, and tissue homeostasis as a consequence of MMPr capacity for breaking down many types of extracellular matrix proteins. Imbalanced regulation of MMP expression can also lead to pathological conditions such as tumor progression. We recently reported that the Drosophila Mmp1 gene is highly expressed in the digestive tract and is required for the maintenance of intestinal homeostasis such as by restriction of uncontrolled intestinal stem cell proliferation. However, the regulatory mechanisms of MMP gene expression in the intestine remain unclear. In this study, we determined that the expression of Mmp1 is regulated by the homeodomain transcription factor Caudal. Experiments using the targeted expression of Caudal under the regulation of Gal4-UAS system indicated that endogenous Caudal is required for the Mmp1 gene expression in the adult Drosophila intestine and that exogenous Caudal induces Mmp1 expression. Transient transfection experiments indicated that Caudal can activate the promoter activity of Mmp1 and that several putative Caudal binding sites in the 5'-flanking region of the Mmp1 gene may be critical to the upregulation by Caudal. Our data suggest that Mmp1 is one of the target genes of Caudal in physiological normal condition and in tumorigenesis.

Matrix metalloproteinase (MMP)는 세포외골격의 주요 조절효소로, 배아발생, 혈관생성, 상처치료 및 조직 재생과정에 중요한 인자로 알려져 있다. MMP의 조절 이상은 비정상적 세포외골격 분해로 인해 암 전이와 같은 질병을 일으킨다. 따라서, MMP의 발현과 활성은 엄격하게 조절되고 있다. 최근, 초파리 Mmp1이 소화기관에서 강하게 발현되며, 장줄기세포의 비정상적인 활성을 억제하여 장의 항상성 유지에 중요함을 밝혔다. 하지만, 장조직에서 Mmp1의 발현 조절 기전은 아직 밝혀지지 않았다. 본 연구에서는, 장조직에서 Mmp1의 발현이 장 발생과 항상성 유지에 중요한 Caudal homeobox 유전자에 의해 조절되는지를 연구하였다. GAL4/UAS 조절계를 이용하여 장조직 특이적으로 Caudal의 발현을 감소시켰을 때, Mmp1의 발현이 감소함을 확인하였으며, Caudal을 과발현 시켰을 때, Mmp1의 발현이 증가함을 in vitro와 in vivo 실험 모두에서 확인하였다. 또한, Mmp1 promoter에 Caudal 전사인자 결합 부위가 존재하며, 이 부위가 Mmp1 발현에 중요한 역할을 함을 확인하였다. 이상의 본 연구는, 정상적 혹은 암화 과정에서 Mmp1이 Caudal의 표적 유전자일 수 있음을 의미한다.

Keywords

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