Childhood Kidney Diseases

Korean Society of Pediatric Nephrology (대한소아신장학회)
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Transcriptome Profiling of Kidney Tissue from FGS/kist Mice, the Korean Animal Model of Focal Segmental Glomerulosclerosis

국소성 분절성 사구체 신병증의 동물 모델 (FGS/kist 생쥐) 신 조직의 유전자 발현 양상

  • Kang, Hee-Gyung (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Lee, Byong-Sop (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Chul-Ho (Animal Model Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Ha, Il-Soo (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Cheong, Hae-Il (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Choi, Yong (Department of Pediatrics, Inje University Haeundae Paik Hospital)
  • 강희경 (서울대학교병원 소아청소년과) ;
  • 이병섭 (울산대학교 의과대학 소아청소년과) ;
  • 이철호 (한국생명공학연구원) ;
  • 하일수 (서울대학교병원 소아청소년과) ;
  • 정해일 (서울대학교병원 소아청소년과) ;
  • 최용 (인제대학교 부산해운대백병원 소아청소년과)
  • Received : 2011.03.19
  • Accepted : 2011.04.15
  • Published : 2011.04.30
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Abstract

Purpose: Focal segmental glomerulosclerosis (FSGS) is the most common glomerulopathy causing pediatric renal failure. Since specific treatment targeting the etiology and pathophysiology of primary FSGS is yet elusive, the authors explored the pathophysiology of FSGS by transcriptome analysis of the disease using an animal model. Methods: FGS/kist strain, a mouse model of primary FSGS, and RFM/kist strain, as control and the parent strain of FGS/kist, were used. Kidney tissues were harvested and isolated renal cortex was used to extract mRNA, which was run on AB 1700 mouse microarray chip after reverse transcription to get the transcriptome profile. Results: Sixty two genes were differentially expressed in FGS/kist kidney tissue compared to the control. Those genes were related to cell cycle/cell death, immune reaction, and lipid metabolism/vasculopathy, and the key molecules of their networks were TNF, IL-6/4, IFN${\gamma}$, TP53, and PPAR${\gamma}$. Conclusion: This study confirmed that renal cell death, immune system activation with subsequent fibrosis, and lipid metabolism-related early vasculopathy were involved in the pathophysiology of FSGS. In addition, the relevance of methodology used in this study, namely transcriptome profiling, and Korean animal model of FGS/kist was validated. Further study would reveal novel pathophysiology of FSGS for new therapeutic targets.

목 적: 국소성 분절성 사구체 경화증(Focal segmental glomerulosclerosis, 이하 FSGS)은 소아신부전의 원인 중 가장 흔한 사구체 질환이다. 일차성 FSGS의 병인은 아직 알려져 있지 않으므로, 저자들은 FSGS의 동물 모델을 대상으로 cDNA 마이크로어레이를 이용한 유전자 발현 양상 분석을 통하여 유전자 발현 수준에서의 FSGS의 질환의 특성을 밝히고자 하였다. 방 법: 사람의 일차성 FSGS와 유사한 질병경과를 보이는 동물모델인 FGS/kist 생쥐의 신피질 조직을 대조군 생쥐(FGS/kist 생쥐의 조상 strain인 RFM/kist 생쥐)와 AB 1700 mouse chip을 이용한 마이크로어레이 실험으로 비교하였다. 결 과: FGS 질병특이 유전자가 62개 추출되었다. 이들은 세포주기/사멸, 면역반응과 지질 대사/혈관 질환과 관련된 유전자들로써, 유전자간 network의 중심유전자가 면역반응(TNF, IL-6/4, IFNg)과 세포사멸 조절 유전자(TP 53), 그리고 지질대사의 중요 유전자인 PPARG이었다. 결 론: 이 연구에서 저자들은 자발적인 FSGS의 임상경과를 보이는 FGS/Kist 생쥐의 신장조직의 유전자 발현의 분석을 통하여 신장세포사멸과 면역반응에 뒤따르는 기질 섬유화, 그리고 지질 대사의 이상과 조기 혈관 질환이 FSGS의 병태생리에 기여할 것임을 다시 확인할 수 있었다. 추가적인 연구가 계속된다면 global transcriptome profiling 기법으로 병인 탐색 및 치료방법 개발 에 의미 있는 결과를 도출할 수 있을 것이다.

Keywords

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