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Differential Expression of Nephrin According to Glomerular Size in Early Diabetic Kidney Disease

Jin-Ju Kim^*, Jin Ji Li^*,, Dong-Sub Jung^*, Seung-Jae Kwak^*, Dong-Ryeol Ryu, Tae-Hyun Yoo^*, Seung Hyeok Han^*, Hoon Young Choi^*, Hyung Jong Kim, Dae Suk Han^* and Shin-Wook Kang^*

^* Department of Internal Medicine, College of Medicine, Brain Korea 21, Yonsei University, Seoul, Korea; Nephrology and Dialysis Unit, Department of Internal Medicine, The Affiliated Hospital, YanBian University Medical College, JiLin, China; Department of Internal Medicine, College of Medicine, Ewha Woman's University, Seoul, Korea; and Department of Internal Medicine, College of Medicine, Pochon CHA University, Sungnam, Korea

Correspondence: Dr. Shin-Wook Kang, Yonsei University College of Medicine, Department of Internal Medicine, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul, Korea, 120-752. Phone: +82-2-2228-1959; Fax: +82-2-393-6884; E-mail: kswkidney{at}yumc.yonsei.ac.kr

Received for publication October 24, 2006. Accepted for publication April 17, 2007.

Diabetic nephropathy (DN) is clinically characterized by proteinuria. Many studies tried to demonstrate a relationship between proteinuria and changes in nephrin in various forms of glomerular diseases including DN, but the results are not consistent. Glomerular hypertrophy occurs in DN, yet hypertrophy does not develop in all glomeruli concurrently. For investigation of the differences in nephrin expression according to glomerular size, glomeruli were isolated from 10 control and 10 streptozotocin-induced diabetic rats at 6 wk after the induction of diabetes by a sieving technique using sieves with pore sizes of 250, 150, 125, and 75 µm. Glomeruli then were classified into large glomeruli (LG; on the 125-µm sieve) and small glomeruli (SG; on the 75-µm sieve) groups. Glomerular volumes were determined using an image analyzer, and mRNA and protein expression was determined by real-time PCR and Western blot, respectively. The mean volumes of diabetic LG (1.51 ± 0.06 x 10⁶ µm³) and control LG (1.37 ± 0.05 x 10⁶ µm³) were significantly higher than those of diabetic SG (0.94 ± 0.03 x 10⁶ µm³) and control SG (0.87 ± 0.03 x 10⁶ µm³; P < 0.01). Nephrin mRNA expression was significantly reduced in the diabetic LG group compared with the diabetic SG and control glomeruli groups (P < 0.05). In contrast, nephrin mRNA expression was significantly higher in the diabetic SG group compared with the diabetic LG and control glomeruli groups (P < 0.05). Even after correction for 18s rRNA and Wilms’ tumor-1 mRNA expression, the differences in nephrin mRNA expression remained significant. The expression of nephrin protein showed a similar pattern to the mRNA expression. In conclusion, these data suggest that the nephrin gene is differentially expressed according to glomerular size. Furthermore, more hypertrophied glomeruli with lesser nephrin expression may be responsible for albuminuria in the early stage of DN.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673