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Radiation Induced Changes in the Expression of Fibronectin, Pai-1, MMP in Rat Glomerular Epithelial Cell  

Park Woo-Yoon (Department of Radiation Oncology, Chungbuk National Univesity)
Kim Won-Dong (Department of Radiation Oncology, Chungbuk National Univesity)
Zheng Ying (Department of Radiation Oncology, Chungbuk National Univesity)
Ha Tae-Sun (Department of Pediatrics, College of Medicine, Chungbuk National University)
Kim Jae-Sung (Department of Radiation Oncology, College of Medicine, Seoul National University)
Cho Moon-June (Department of Radiation Oncology, College of Medicine, Chungnam National University)
Publication Information
Radiation Oncology Journal / v.24, no.1, 2006 , pp. 58-66 More about this Journal
Abstract
Purpose: 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. Materials and Methods: 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). Results: 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. Conclusion: 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.
Keywords
Rat glomerular epithelial cell; Radiation; Fibronectin; Pai-1; MMP;
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1 van Det NF. Verhagen NA, Tamsma JT, et al. Regulation of glomerular epithelial cell production of fibronectin and transforming growth factor-beta by high glucose, not by angiotensin II. Diabetes 1997;46:834-840   DOI   ScienceOn
2 Adler S. Characterization of glomerular epithelial cell matrix receptors. Am J Patho 1992;141:571-578
3 Weichselbaum RR, Hallahan D, Fuks Z, Kufe D. Radiation induction of immediate early genes; effectors of the radiationstress response. Int J Radiat Oncol Biol Phys 1994;30:229-234   DOI   ScienceOn
4 Wegrowski J, Remy J, Martin M, Lafuma C. Fibronectin and glycosaminoglycan synthesis by fibrotic pig fibroblasts in primary culture. Connect Tissue Res 1989;23:237-249   DOI
5 Wang J, Robbins MEC. Radiation-induced alteration of rat mesangial cell transforming growth factor-beta and expression of the genes associated with the extracellular matrix. Radiat Res 1996;146:561-568   DOI
6 Gunja-Smith Z, Morales AR, Romanelli R. Woessner JF Jr. Remodeling of human myocardial collagen in idiopathic dilated cardiomyopathy: role of metalloproteinases and pyridinoline cross-links. Am J Pathol 1996;148:1639-1648
7 Oikawa T, Freeman M, Lo W, Vaughan DE, Fogo A. Modulation of plasminogen activator inhibitor-1 in vivo: a new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition. Kidney Int 1997:51:164-172   DOI   ScienceOn
8 Birkedal-Hansen H, Moore WG, Bodden MK, et al. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 1993;4:197-250   DOI
9 Robbins ME, O'Malley Y, Zhao W, Davis CS. Bonsib SM. The role of the tubulointerstitium in radiation-induced renal fibrosis. Radiat Res 2001;155:481-489   DOI   ScienceOn
10 Zhao W. O'Malley Y. Wei S. Robbins ME. Irradiation of rat tubule epithelial cells alters the expression of gene products associated with the synthesis and degradation of extracellular matrix. Int J Radiat Biol 2000;76:391-402   DOI
11 Kreisberg JI, Karnovsky MJ. Glomerular cells in culture. Kidney Int 1983;23:439-447   DOI   ScienceOn
12 Odekon LE. Blasi F, Rifkin DB. Requirement for receptorbound urokinase in plasmin-dependent cellular conversion of latent TGF-beta to TGF-beta. J Cell Physiol 1994;158:398-407   DOI   ScienceOn
13 Finkelstein JN, Johnston CJ, Baggs R, Rubin P. Early alterations in extracellular matrix and transforming growth factor beta gene expression in mouse lung indicative of late radiation fibrosis. Int J Radiat Oncol Biol Phys 1994;28:621-631   DOI   ScienceOn
14 Seftor EA. Electrophoretic analysis of proteins associated with tumor cell invasion. Electrophoresis 1999;15:454-462   DOI   ScienceOn
15 Ts'ao C. Ward WF. Acute radiation effects on the content and release of plasminogen activator activity in cultured aortic endothelial cells. Radiat Res 1985;101:394-401   DOI
16 Sawaya R, Tofilon PJ, Mohanam S, et al. Induction of tissue-type plasminogen activator and 72-kDa type-IV collagenase by ionizing radiation in rat astrocytes. Int J Cancer 1994;56:214-218   DOI   ScienceOn
17 Lafuma C, EI Nabout RA. Crechet F. Hovnanian A, Martin M. Expression of 72-kDa gelatinase (MMP-2), collagenase (MMP-1), and tissue metalloproteinase inhibitor (TIMP) in primary pig skin fibroblast cultures derived from radiation-induced skin fibrosis. J Invest Dermatol 1994;102:945-950   DOI   ScienceOn
18 Woloschak GE, Felcher P. Chang-Liu CM. Expression of cytoskeletal and matrix genes following exposure to ionizing radiation: dose-rate effects and protein synthesis requirements. Cancer Lett 1995;92: 135-141   DOI   ScienceOn
19 Zhao W. O'Malley Y. Robbins MEC. Irradiation of rat mesangial cells alters the expression of gene products associated with the development of renal fibrosis. Radiat Res 1999;152: 160-169   DOI
20 Butler GS, Butler MJ, Atkinson SJ, et al. The TIMP2 membrane type 1 metalloproteinase receptor regulates the concentration and efficient activation of progelatinase A: a kinetic study. J Biol Chem 1998;273:871-880   DOI   ScienceOn
21 Stewart FA. Radiation nephropathy after abdominal irradiation or total body irradiation. Radiat Res 1995;143:235-237   DOI
22 Carome MA. Striker LJ. Peten EP. et al. Human glomeruli express TIMP-1 mRNA and TIMP-2 protein and mRNA. Am J Physiol 1993;264:F923-F929
23 McMillan JI. Riordan JW. Couser WG, Pollock AS. Lovett DH. Characterization of a glomerular epithelial cell metalloproteinase as matrix metalloproteinase-9 with enhanced expression in a model of membranous nephropathy. J Clin Invest 1996;97:1094-1101   DOI   ScienceOn
24 Mentzel S, Van Son JP, De Jong AS, et al. Mouse glomerular epithelial cells in culture with features of podocytes in vivo express aminopeptidase A and angiotensinogen but not other components of the renin-angiotensin system. J Am Soc Nephro 1997;8:706-719
25 Avioli LV, Lazor MZ. Cotlove E. Brace KC. Andrews JR. Early effects of radiation on renal function in man. Amer J Med 1963;34:329-337   DOI   ScienceOn