The Effect of Tumor Necrosis Factor-Alpha on Glomerular Epithelial Cells in Glomerular Permeability
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목 적:미세변화신증후군은 소아의 원발성 신증후군의 주요 원인질환이다. 미세변화증후군의 정확한 병인기전은 아직까지 알려져 있지 않으나, 최근 TNF-α가 이 질환의 병인기전과 관련된다는 보고가 있었다. 이에 저자들은 환아의 혈청과 요에서 TNF-α의 변화를 살펴보고, TNF-α가 이 질환의 표적세포인 토리 상피세포에 미치는 직접적인 영향을 알아보고자 본 연구를 시행하였다. 방 법:2-15세의 미세변화신증후군 환아에게서 혈청과 요에서 TNF-α치를 측정하였고, 토리 상피세포로 도포된 Millicell system을 사용하여 TNF-α가 토리 상피세포에 의하여 형성되는 투과성에 미치는 영향을 알아보았다. 또한 TNF-α가 토리 상피세포에서 생성되어 토리 기저막의 투과성을 결정하는 물질인 heparan sulfate proteoglycan의 유전자 발현과 생성에 미치는 영향을 측정하였다. 결 과:미세변화신증후군의 재발시 요중 TNF- α치 (ng/mg․cr)는 364.4±51.2로서 관해와 대조군의 155.3±20.8과 36.0±4.5에 비하여 유의하게 증가되어 있었다 (P<0.05). 그러나 TNF-α가 토리 상피세포의 투과성 검사와 토리 상피세포의 heparan sulfate proteoglycan의 유전자 발현과 생성에 아무런 영향을 미치지 않았다. 결 론:TNF-α는 토리 상피세포에 직접적인 영향을 미치지 않으므로 미세변화신증후군에서의 요중 TNF-α치의 증가는 질병으로 인한 이차적인 변화일 것으로 생각된다.
Abstract
Purpose : Minimal Change Disease (MCD) is the most common primary nephrotic syndrome in children. Some suggested that tumor necrosis factor-α (TNF-α) are involved in the pathogenesis of MCD.Methods : This study was done to see the changes of plasma and urinary TNF-α, and its effect on the determination of permeability of the glomerular basement membrane (BM) contributed by heparan sulfate proteoglycan (HSPG). Study patients consisted of 19 biopsy- proven MCD children aged 2-15 years old. Both plasma and urinary TNF-α were measured. Employing the Millicell system, TNF-α was screened for the permeability factors. We examined whether TNF-α regulated BM HSPG gene expression and HS synthesis in the glomerular epithelial cells (GECs). Results : Urinary TNF-α during relapse was significantly increased when compared with that of during remission or controls (364.4±51.2 vs 155.3±20.8, 36.0±4.5 ng/mg·cr) (P< 0.05). However, negative results were obtained in the permeability assay using the Millicell system. No difference was seen in the BM HSPG gene expression and HS synthesis in the GECs. Conclusion : It seems that TNF-α may not play a disease-specific role in the pathogenesis of MCD.
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