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J Korean Soc Ther Radiol Oncol > Volume 24(1); 2006 > Article
The Journal of the Korean Society for Therapeutic Radiology and Oncology 2006;24(1): 58-66.
Radiation Induced Changes in the Expression of Fibronectin, Pai-1, MMP in Rat Glomerular Epithelial Cell
Woo Yoon Park, Won Dong Kim, Ying Zheng, Tae Sun Ha, Jae Sung Kim, Moon June Cho
1Department of Radiation Oncology, Chungbuk National University, Cheongju, Korea. wynpark@chungbuk.ac.kr
2Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju, Korea.
3Medical Research Institute, Chungbuk National University, Cheongju, Korea.
4Department of Radiation Oncology, College of Medicine, Seoul National University, Seoul, Korea.
5Department of Radiation Oncology, College of Medicine, Chungnam National University, Daejeon, Korea.
Renal irradiation can lead to the development of radiation nephropathy, and this is characterized by the accumulation of extracellular matrix and final fibrosis. To determine the possible role of the glomerular epithelial cell, the radiation-induced changes in the expression of its genes associated with the extracellular matrix were analyzed.
Rat glomerular epithelial cells (GEpC) were irradiated with a single dose of 0, 2, 5, 10 and 20 Gy with using 6 MV LINAC (Siemens, USA), and the samples were collected 6, 24, 48 and 72 hours post-irradiation, respectively. Northern blotting, western blotting and zymography were used to measure the expression level of fibronectin (Fn), plasminogen activator inhibitor-1 (Pai-1), matrix metalloproteinases-2, 9 (MMP-2, 9), tissue inhibitor of metalloproteinase-2 (TIMP-2), tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA).
Irradiation with a single dose of 10 Gy resulted in a significant increase in Fn mRNA since 24 hours post-irradiation, and a single dose of 5 and 10 Gy significantly increased the Fn immunoreactive protein measured 48 hours post-irradiation. An increase in Pai-1 mRNA and protein was also observed and especially, a single dose of 10 Gy significantly increased the mRNA measured 24 and 48 hours post-irradiation. The active MMP-2 measured 24 hours post-irradiation slightly increased in a dose dependent manner, but this increase did not reach statistical significance. The levels of MMP-9, TIMP-2, t-PA and u-PA appeared unaltered after irradiation.
Irradiation of the glomerular epithelial cells altered the expression of genes associated with the extracellular matrix, implying that the glomerular epithelial cell may be involved in the development of radiation nephropathy.
Key Words: Rat glomerular epithelial cell, Radiation, Fibronectin, Pai-1, MMP
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