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

 Beom Seok Kim  ;  Hyeong Cheon Park  ;  Shin Wook Kang  ;  Kyu Hun Choi  ;  Sung Kyu Ha  ;  Dae Suk Han  ;  Ho Yung Lee 
 YONSEI MEDICAL JOURNAL, Vol.46(1) : 141-148, 2005 
Journal Title
Issue Date
Nephrotic syndrome ; PAN nephrosis ; ZO-1 ; Cyclosporin
Nephrotic syndrome ; PAN nephrosis ; ZO-1 ; Cyclosporin
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kim, Beom Seok(김범석) ORCID logo https://orcid.org/0000-0002-5732-2583
Park, Hyeong Cheon(박형천) ORCID logo https://orcid.org/0000-0002-1550-0812
Lee, Ho Yung(이호영)
Choi, Kyu Hun(최규헌) ORCID logo https://orcid.org/0000-0003-0095-9011
Ha, Sung Kyu(하성규)
Han, Dae Suk(한대석)
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