Address of Corresponding Author

Nephron Exp Nephrol 2006;103:e16-e26 (DOI: 10.1159/000090504)

  Key Words

• Connective tissue growth factor
• Angiotensin II
• Hypertrophy
• Renal tubular cell

  Abstract

Background: Cellular hypertrophy is an early, important pathological feature of renal diseases such as diabetic nephropathy and remnant kidney. Recent studies have demonstrated that angiotensin II (AngII) plays a key role in mediating cell hypertrophy. The aim of our work was to explore the role of connective tissue growth factor (CTGF) in mediating AngII-induced tubular cell hypertrophy in vivoandin vitro. Methods: In an in vivo study, male Sprague-Dawley rats were randomly divided into three groups: control rats, diabetic rats and diabetic rats treated with irbesartan (IRB). The index of kidney hypertrophy (kidney weight/body weight, KW/BW), glomerular tuft area (A_G), glomerular tuft volume (V_G) and proximal tubular area (A_T) were determined. Renal expression for CTGF was detected by immunohistochemical staining. In an in vitro study, the influence of CTGF antisense oligonucleotide (CTGF AS) on AngII-induced CTGF expression and cell hypertrophy was also investigated. Results:In an in vivo study, diabetic rats showed a significant increase of KW/BW, A_G, V_G, and A_T from week 1 onwards compared to normal control, which could be significantly inhibited by using IRB. Furthermore, there was a significantly increasing expression of CTGF in both glomeruli and tubuli in diabetic rats compared to control, and the extent of CTGF expression closely correlated with the severity of renal hypertrophy. Treatment with IRB could markedly inhibit the renal expression of CTGF. In an in vitro study, AngII stimulated the expression of CTGF mRNA and CTGF protein. AngII significantly increased the total protein content in HK2 cells, which was markedly inhibited by co-treatment with CTGF AS. The average cellular diameter determined by scanning electronic microscope showed that the increase of cell size induced by AngII could be significantly inhibited by CTGF AS. Furthermore, flow cytometer study showed that AngII arrested the cell cycle in the G0-G1 phase, which was significantly reversed by treatment with CTGF AS. Conclusion: Our data provide both in vivo and in vitroevidence that CTGF is involved in mediating AngII-induced renal hypertrophy.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Prof. Bi-Cheng Liu, MD, PhD
Institute of Nephrology, Zhong Da Hospital
Southeast University School of Medicine
Nanjing 210009 (China)
Tel./Fax +86 25 8327 2090, E-Mail liubc64@yahoo.com.cn

  Article Information

Received: May 26, 2005
Accepted after revision: September 27, 2005
Published online: December 21, 2005
Number of Print Pages : 11
Number of Figures : 6, Number of Tables : 7, Number of References : 31