Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Downregulation of SGK1 Expression is Critical for TGF-β-induced Apoptosis in Mouse Hepatocytes Cells

TGF-β에 의한 간세포의 세포사멸 과정에서 SGK1 발현 감소의 중요성

  • Nam, In-Koo (Department of Microbiology/Research Institute of Life Science, College of Natural Sciences, Gyeongsang National University) ;
  • Yoo, Jiyun (Department of Microbiology/Research Institute of Life Science, College of Natural Sciences, Gyeongsang National University)
  • 남인구 (경상대학교 자연과학대학 미생물학과/생명과학연구원) ;
  • 유지윤 (경상대학교 자연과학대학 미생물학과/생명과학연구원)
  • Received : 2012.09.05
  • Accepted : 2012.11.21
  • Published : 2012.11.30
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Abstract

Transforming growth factor (TGF)-${\beta}$-dependent apoptosis is important in the elimination of damaged or abnormal cells from normal tissues, especially in liver, in vivo. To investigate which gene expressions are critical for TGF-${\beta}$-induced apoptosis in hepatocytes, gene expression profiling experiments were performed with TGF-${\beta}$-treated and non-treated mouse hepatocytes AML12 cells. Findings showed that serum and glucocorticoid-inducible protein kinase1 (SGK1) expression is markedly downregulated during TGF-${\beta}$-induced apoptosis. Findings confirmed that expression of SGK1 protein, as well as mRNA, is also markedly decreased with TGF-${\beta}$ treatment. Infection of adenoviral vector encoding constitutively active SGK1 (CA-SGK1), but not kinase dead SGK1 (KD-SGK1), attenuated TGF-${\beta}$-induced apoptosis. All of these results suggest that downregulation of SGK1 expression is critical for TGF-${\beta}$-induced apoptosis in AML12 cells.

Transforming growth factor-${\beta}$ (TGF-${\beta}$)에 의해 유도되는 세포사멸 과정은 간에서 손상 받은 조직이나 비정상적인 조직을 제거하는데 중요한 역할을 담당한다. 간세포에서 TGF-${\beta}$에 의해 유도되는 세포사멸 과정 동안 중요한 기능을 담당하는 유전자를 탐색하고자 쥐의 간세포인 AML12 세포를 이용하여 TGF-${\beta}$ 처리 전후에 발현이 변화되는 유전자를 microarray analysis를 통해 확인하였다. TGF-${\beta}$에 의해 여러 가지 유전자들의 발현이 변화됨을 확인하였는데, 그 가운데 여러 가지 세포사멸 인자들의 활성을 억제하여 세포사멸을 억제한다고 알려져 있는 SGK1의 발현 감소를 확인하였다. TGF-${\beta}$에 의해 SGK1의 mRNA와 단백질 level이 모두 감소함을 확인하였고, 항상 active한 형태의 SGK1 (CA-SGK1)을 발현시켰을 때 TGF-${\beta}$에 의한 세포사멸이 억제됨을 확인하였다. 이러한 결과들은 간세포에서 SGK1의 발현 감소가 TGF-${\beta}$에 의한 세포사멸을 유도하는데 중요한 기능을 담당할 가능성이 높음을 의미하는 것이다.

Keywords

References

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