Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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The Expression of MMPs and TIMPs in IPF and NSIP

IPF와 NSIP에서 MMPs와 TIMPs의 발현

  • Kim, Yu Jin (Division of Pulmonary Medicine, Department of Internal Medicine, Gachon Medical School Gil Medical Center) ;
  • Kim, Jung Ho (Division of Pulmonary Medicine, Department of Internal Medicine, Gachon Medical School Gil Medical Center) ;
  • Jeon, Hyo Keun (Division of Pulmonary Medicine, Department of Internal Medicine, Gachon Medical School Gil Medical Center) ;
  • Kim, Mi Kyeong (Division of Pulmonary Medicine, Department of Internal Medicine, Gachon Medical School Gil Medical Center) ;
  • Jo, Young Chan (Division of Pulmonary Medicine, Department of Internal Medicine, Gachon Medical School Gil Medical Center) ;
  • Kyung, Sun Yong (Division of Pulmonary Medicine, Department of Internal Medicine, Gachon Medical School Gil Medical Center) ;
  • An, Chang Hyeok (Division of Pulmonary Medicine, Department of Internal Medicine, Gachon Medical School Gil Medical Center) ;
  • Lee, Sang Pyo (Division of Pulmonary Medicine, Department of Internal Medicine, Gachon Medical School Gil Medical Center) ;
  • Park, Jung Woong (Division of Pulmonary Medicine, Department of Internal Medicine, Gachon Medical School Gil Medical Center) ;
  • Ha, Seung Yeon (Department of Pathology, Gachon Medical School Gil Medical Center) ;
  • Jeong, Sung Hwan (Division of Pulmonary Medicine, Department of Internal Medicine, Gachon Medical School Gil Medical Center)
  • 김유진 (가천의대 길병원 호흡기내과) ;
  • 김정호 (가천의대 길병원 호흡기내과) ;
  • 전효근 (가천의대 길병원 호흡기내과) ;
  • 김미경 (가천의대 길병원 호흡기내과) ;
  • 조용찬 (가천의대 길병원 호흡기내과) ;
  • 경선영 (가천의대 길병원 호흡기내과) ;
  • 안창혁 (가천의대 길병원 호흡기내과) ;
  • 이상표 (가천의대 길병원 호흡기내과) ;
  • 박정웅 (가천의대 길병원 호흡기내과) ;
  • 하승연 (가천의대 길병원 병리과) ;
  • 정성환 (가천의대 길병원 호흡기내과)
  • Received : 2006.08.09
  • Accepted : 2006.10.18
  • Published : 2006.11.30
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Abstract

Background: MMPs and TIMPs are important factors for abnormal remodeling the pulmonary parenchyme in idiopathic interstitial pneumonia(IIP) This study evaluated the expression of MMPs and TIMPs in the tissue of IPF, NSIP and normal control subjects. Method: The MMP-2 and -9 activity in the lung tissue was studied by gelatin zymography, and the expression of MMP-1, -2, -9, TIMP-1 and -2 in the lung tissue was measured by immunohistochemistry. Thirty five patients, who were diagnosed with IIP (UIP ; 22, NSIP ; 13), were enrolled in the immunohistochemical study. Thirteen patients with IIP (UIP ; 9, NSIP ; 4) and five patients with lung cancer were enrolled in the zymographic assay. Results: (1) The immunohistochemistry for MMP-1,-2,-9, TIMP-1 and-2 ; MMP-1,-9 and TIMP-2 were stained stronger in the UIP subjects than NSIP and the normal control. TIMP-2 was strongly stained in the UIP tissue. particularly the fibroblasts in the fibroblastic foci. (2) Zymography for MMP-2 and MMP-9 revealed MMP-2 to have prominent expression in the UIP tissue than in the NSIP tissue. Conclusions: These results suggest that the overexpression of the TIMPs and gelatinases in UIP might be important factors in the irreversible fibrosis of the lung parenchyme.

연구배경: 특발성 폐섬유화증/통상형 간질성 폐렴은 특발성 간질성 폐렴 중 하나로 세포외 기질의 과도한 침착과 기저막 파괴를 통해 섬유모세포/ 근섬유모세포가 폐포 내로 이동하면서 발생하는 fibroblast foci가 대표적인 병리학적 현상이며, 결국 비가역적인 섬유화로 진행하는 질환이다. 이에 대하여 기질 분해효소인 MMPs와 그 길항체인 TIMPs의 과발현이 이러한 병태생리의 한 요인으로 설명되고 있다. 본 연구에서는 특발성 폐섬유화증/통상형 간질성 폐렴을 비롯, 비특이성 간질성 폐렴에서 MMPs와 TIMPs의 발현 양상을 살펴보고자 하였다. 연구방법: 특발성 폐섬유화증/통상형 간질성 폐렴, 비특이성 간질성 폐렴의 폐 조직을 이용하여 MMP-1,-2,-9, TIMP-1, -2에 대한 면역조직화학염색 검사와 MMP-2, MMP-9에 대한 gelatin zymography를 시행하였다. 면역조직화학염색 검사는 통상형 간질성 폐렴 22, 비특이성 간질성 폐렴 13례 였으며, gelatin zymography는 통상형 간질성 폐 렴 9, 비특이성 간질성 폐렴 4례, 정상 대조군5례였다. 연구결과: 면역조직화학 염색 검사 결과 섬유모세포/근섬유모세포 부위에서 TIMP-1, -2, MMP-2,9이 관찰 되었고, 특히 통상형 간질성 폐렴에서 비특이성 간질성 폐렴보다 TIMP-2가 강하게 발현되었다. Gelatin zymography 결과는 MMP-2, MMP-9 모두 통상형 간질성 폐렴에서 비특이성 간질성 폐렴보다 유의하게 높은 소견을 보여 주었다. 결 론: 통상형 간질성 폐렴 에서 비특이성 간질성 폐렴보다 TIMP-2, MMP-2, MMP-9의 과발현을 관찰할 수 있었으며, 이는 통상형 간질성 폐렴의 비가역적인 섬유화 진행에 관여할 가능성이 있음을 추측해 볼 수 있다.

Keywords

References

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