A Possible Role of Thioredoxin Interacting Protein in the Pathogenesis of Streptozotocin-induced Diabetic Nephropathy
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概要
- 論文の詳細を見る
Oxidative stress has been suggested to play an important role in the pathogenesis ofdiabetic nephropathy because it increases under diabetic conditions and is known toinduce cellular dysfunction in a wide variety of cells. To protect cells against oxidativestress, cells possess defensive mechanisms such as intracellular antioxidants. Althoughit has been reported that central enzymes in the antioxidative defense mechanisms ofthe cell are induced under hyperglycemic conditions, the oxidative stress level remainshigh. On the other hand, there are endogenous inhibitors of antioxidants, such asthioredoxin interacting protein (Txnip). In the present study, the relationship betweendiabetic nephropathy and Txnip was investigated using streptozotocin (STZ)-induceddiabetic mice. Eight-week-old male C57BL/6 mice were treated with either STZ orcitrate vehicle. After 24 weeks of treatment, diabetic nephropathy and oxidative stresswere assessed by biochemical analyses of urine and histological analyses of the kidneys.In addition, the expression of Type IV collagen α1 chain (Col4A1), Transforminggrowth factor-β (TGF-β), and Txnip were evaluated by real-time polymerase chainreaction. Albuminuria, renal hypertrophy, and expansion of the mesangial area, whichare the hallmarks of diabetic nephropathy, were confirmed in the diabetic mice. ThemRNA expression of COL4A1 and TGF-β was dramatically increased in diabetic micein comparison with the control mice. Moreover, associated with the increased renalexpression of Txnip, diabetic conditions increased oxidative stress as determined byurinary excretion of 8-hydroxy-2'-deoxyguanosine and acrolein adduct, which areoxidative stress markers. Moreover, Txnip may be a therapeutic target in diabeticnephropathy.
- 神戸大学の論文
著者
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FUKAGAWA Masafumi
Division of Nephrology and Kidney Center, Kobe University School of Medicine
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HAMADA Yasuhiro
Division of Nephrology and Dialysis Center, Kobe University School of Medicine
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Fukagawa Masafumi
Division Of Nephrology And Dialysis Center Kobe University Graduate School
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Fukagawa Masafumi
Division Of Nephrology And Dialysis Center Kobe University Graduate School Of Medicine
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Hamada Yasuhiro
Division Of Nephrology And Dialysis Center Kobe University Graduate School Of Medicine
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