대한신장학회

논문분류	춘계학술대회 초록집
제목	The Expression of Full Length MMP-2 and Intracellular N-terminal Truncated MMP-2 Isoform in Diabetic Kidney Disease
저자	Su Min Park1, Sang Heon Song1, Ihm Soo Kwak1, Min Young Lee1, Eun Young Seong1, Harin Rhee1, Il Young Kim1, Dong Won Lee1, Soo Bong Lee1, Woo Jin Jung1, Jong Man Park1, Su Jeung Kim2, Young Ji Beack2, Kyeongjoo Park2, David H. Lovett3
출판정보	2015; 2015(1):
키워드	당뇨병성 신증,전장 MMP-2,N-말단 결실 MMP-2
초록	Background: Recently, matrix metalloproteinase-2 has been regarded as a central of injury mechanism in heart and kidney. The ultrastructural examination of MMP-2 transgenic renal tubular epithelial cells demonstrated mitochondrial structural alterations and subsequent investigation led to the discovery of a novel intracellular N-terminal truncated isoform of MMP-2 (NTT-MMP-2) generated by activation of an alternative intronic promoter. The aim of this study is to explore the expression pattern and the role of full length MMP-2 (FL-MMP-2) and NTT-MMP2 in diabetic kidney disease. Method: In vitro study, we tested glucose stimulation effects on HK2 cells. High, moderate, normal glucose were 30 mM, 15 mM, 5.6 mM. Time dependent experiments for 2hr, 24hr, 48hr, 72hr were conducted and dose-dependent experiments for normal, high and cyclic for the time of 48hr were performed. Also, real-time PCR was done for quantitative analysis of FL-MMP-2 and NTT-MMP-2. Results: In vitro study using HK2 cells, high glucose stimulation induced the expression of FL-MMP-2 according to time and the expression at 72hr was higher by 3.4 times compared with control cells. Although the expression of NTT-MMP-2 was increased by high glucose, the peak expression time was different with FL-MMP-2 and the expression at 2hr was higher by 3.4 times compared with control cells. Also, the expression of NTT-MMP-2 was decreased according to time after 2hr stimulation. In dose-dependent experiments, cyclic stimulation induced higher expression of FL-MMP-2 and NTT-MMP-2 compared with control cells (FL-MMP-2; control vs. cyclic 1:4.16, NTT-MMP-2; control vs. cyclic 1:2.13). In streptozotocin-induced diabetic mice, the expression of FL-MMP-2 and NTT-MMP-2 was increased diffusely in the cytoplasm in renal tubular cell compared with normal control mice. In detail, FL-MMP-2 was expressed constitutively and the intensity or stained area were increased by induction of diabetes. However, NTT-MMP-2 was not expressed in normal control mice and was highly expressed after induction of diabetes mainly in renal cortex. Conclusion: Glucose stimulation induced the expression of full length MMP-2 and intracellular N-terminal truncated MMP-2 isoform in HK2 cell. Furthermore, experimental diabetes influenced on full length MMP-2 expression and induced intracellular N-terminal truncated MMP-2 isoform in animal model.
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