Connective tissue growth factor is associated with the early renal hypertrophy in uninephrectomized diabetic rats.
BACKGROUND
Renal hypertrophy has been regarded as the early feature of diabetic nephropathy (DN), which may eventually lead to proteinuria and renal fibrosis. However, the exact mechanism of renal hypertrophy is still unclear. The aim of this study was to investigate the possible association of connective tissue growth factor (CTGF) with renal hypertrophy in uninephrectomized diabetic rats.


METHODS
Seventy-two Sprague-Dawley (SD) rats were randomly divided into two groups: control group (group C, n = 32) and diabetic nephropathy (group DN, n = 40). Each group was re-divided into 4 subgroups according to the experimental period. The rats were sacrificed at 1, 2, 4, and 8 weeks respectively after induction of diabetes. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) after rats had received uninephrectomy. Blood glucose (BG), body weight (BW), 24-h urinary albumin excretion (24hUalb), kidney weight (KW), KW/BW, glomerular tuft area (AG), glomerular tuft volume (VG), proximal tubular area (AT) at each time point, the width of glomerular basement membrane (GBM) and tubular basement membrane (TBM) at week 8 were measured when the rats were sacrificed. Renal expression of CTGF and p27kip1 were detected by immunohistochemical staining. The relationship between CTGF expression and increasing of VG and AT was analyzed.


RESULTS
There was a significant increase of 24hUalb, KW, and KW/BW from week 1 onward in diabetic rats compared to those in group C (P < 0.05, respectively), diabetic rats also had a significant increase of AG, VG, and AT from week 1 onward. It was also shown that diabetic rats had a thickening of GBM [(245.7 +/- 103.0) nm vs (121.8 +/- 19.1) nm, P < 0.01] and TBM [(767.7 +/- 331.1) nm vs (293.0 +/- 110.5) nm, P < 0.01] at week 8. There was a weak expression for CTGF and p27kip1 in normal glomeruli and tubuli, while a significant increasing expression of CTGF and p27kip1 was found in glomeruli and tubuli in diabetic kidney from week 1 onward (P < 0.05, respectively), and the extent of CTGF expression was positively correlated with AG (r = 0.92, P < 0.05), VG (r = 0.86, P < 0.05), AT (r = 0.94, P < 0.01) and positively correlated with the expression of p27kip1 (r = 0.96, P < 0.01).


CONCLUSIONS
The expression of CTGF increases in diabetic rat kidney at the early stage, which might be an important mediator of renal hypertrophy through arresting cell cycling.
Liu
Bi-cheng
BC
Institute of Nephrology, Zhong Da Hospital, Southeast University, Nanjing 210009, China. liubc64@yahoo.com.cn
Huang
Hai-quan
HQ
Luo
Dong-dong
DD
Ma
Kun-ling
KL
Liu
Dian-ge
DG
Liu
Hong
H
D000419:Albuminuria / Q000209:etiology; D000818:Animals; D055513:Connective Tissue Growth Factor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D006984:Hypertrophy; D017874:Immediate-Early Proteins / Q000032:analysis / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000502:physiology*; D007668:Kidney / Q000473:pathology*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
C526316:CCN2 protein, rat; C493962:Cdkn1b protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D013311:Streptozocin