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Impact of Cyclosporin on Podocyte ZO-1 Expression in Puromycin Aminonucleoside Nephrosis Rats

Yonsei medical journal v.46 no.1 , 2005년, pp.141 - 148  
Kim, Beom Seok (Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease, Yonsei University College of Medicine, Seoul, Korea. ) ;  Park, Hyeong Cheon ( Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease, Yonsei University College of Medicine, Seoul, Korea. ) ;  Kang, Shin Wook ( Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease, Yonsei University College of Medicine, Seoul, Korea. ) ;  Choi, Kyu Hun ( Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease, Yonsei University College of Medicine, Seoul, Korea. ) ;  Ha, Sung Kyu ( Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease, Yonsei University College of Medicine, Seoul, Korea. ) ;  Han, Dae Suk ( Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease, Yonsei University College of Medicine, Seoul, Korea. ) ;  Lee, Ho Yung ( Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease, Yonsei University College of Medicine, Seoul, Korea.)
Abstract

Puromycin aminonucleoside (PAN)-induced nephrosis is a well-described model of human idiopathic nephrotic syndrome, but the mechanism of PAN's effect is not completely understood. To investigate whether proteinuria in the PAN model is associated with an alteration of zonula occludens-1 (ZO-1) expression within the glomeruli, and whether cyclosporin A (CsA) has an effect on proteinuria and ZO-1 expression in this model, eighteen Sprague Dawley (SD) rats were assigned into three groups. Twelve rats received a single intraperitoneal injection of PAN (15 mg/100 g). The other six rats received an equal volume of saline (normal control group; control). CsA solution was administered intraperitoneally once a day for 20 days after the PAN injection (n=6, PAN+CsA). The remaining six rats received PAN, but they didn't receive CsA (n=6, PAN). Compared to control rats (35.1 ± 5.4 mg/day), the 24-hour urinary protein excretion on day 18 was significantly higher in the PAN rats (1021.9 ± 128.9 mg/day, p<0.01), and the CsA treatment partly reversed the increase in proteinuria in the PAN rats (556.4 ± 102.3 mg/day, p<0.05). Glomerular ZO-1 protein expressions were significantly increased in the PAN rats as compared to the control group on day 20 (176%, p<0.01). CsA treatment for 20 days in the PAN rats inhibited the increase in ZO-1 protein expression by 71.1% (p<0.05). CsA treatment significantly diminished the glomerular ZO-1 expression in the PAN rats as assessed by immunohistochemistry. CsA treatment significantly reduced proteinuria and the diminished glomerular ZO-1 expression in a PAN nephrosis rat model. These findings suggest the potential role of the slit diaphragm associated proteins in the development of the nephrotic syndrome, and CsA decreased the proteinuria probably by a direct action on the expression of these proteins in podocytes. Further investigations are needed to clarify the role of slit diaphragm associated proteins in the development of PAN nephrosis.

주제어

#Nephrotic syndrome   #PAN nephrosis   #ZO-1   #Cyclosporin  

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