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KMID : 0371620010160010025
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Journal of Wonkwang Medical Science
2001 Volume.16 No. 1 p.25 ~ p.38
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Effect of High Glucose Concentration and PDGF Recepter Inhibitor on Mesangial Cells
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Hyoung Keon-Young
Park Byoung-Hyun
Park Seung-Taeck
Cho Chung-Gu
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Abstract
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Background : Diabetic nephropathy is characterized by hypertrophy of both glomerular and tubular elements, thickening of the glomerular and tubular basement membranes, progressive accumulation of extracellular matrix components in mesangial cells, and tubulointerstitial fibrosis. Hyperglycemia increases the level of diacylglycerol(DAG) and activates protein kinase C(PKC) in mesangial cells and other vascular tissues. PKC activation regulates a number of vascular functions such as vascular permeability, contractility, cellular proliferation, basement membrane synthesis, signal transduction mechanisms for hormones and growth factors. In addition, glomerular mesangial cells play an important role in the development of diabetic nephropathy. Mesangial cells have several functions such as contractile properties, phagocytosis of macromolecules, synthesis of matrix proteins, and production and response to growth factors like platelet derived growth factor(PDGF), transforming growth factor-β(TGF-β). Also, these growth factors play important roles in mesangial cell proliferation and pathophysiology of diabetic nephropathy. Specifically, TGF-β is a key mediator in development of diabetic nephropathy.
Methods : In order to clarify the effect of high glucose concentration and the relation- ship between PDGF and TGF-β on mouse mesangial cell proliferation, hyperglycemia was induced by the addition of high glucose to medium containing mesangial cells derived from neonatal mouse. The effect of high glucose was assessed by the cell proliferation, after mesangial cells were induced with various concentrations of glucose for 48 hours. The effect of TGF-β and PDGF on cell proliferation was examined and the effect of an inhibitor of PDGF and its receptor, suramin was also examined.
Results : 1. LC_50 was a concentration of 20mM glucose when mesangial cells were cultured for 48 hours. 2. Hyperglycemia decreased cell number after mesangial cells were incubated for 48 hours with media containing 20-25 mM glucose, respectively. 3. TGF-β increased cell number dose-dependently. 4. PDGF induced a significant cell proliferation, but suramin, an inhibitor of PDGF receptor decreased in cell number in dose-dependently. 5. In the cell number, suramin decreased in number of mesangial cells against TGF-β induced cell proliferation.
Conclusion : High glucose induced toxic effect, so it was manifestated by decreased number of cultured mesangial cells, and PDGF receptor inhibitor decreased cell proliferation which increased by TGF-β in high glucose. This means PDGF may modulate TGF-β effect on mouse mesangial cell proliferation in high glucose concentration.
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KEYWORD
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Platelet derived growth factor(PDGF), Mesangial cell
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