[Expression and implication of tissue transglutaminase and connective tissue growth factor at fibrotic tubulointerstitium in kidneys from UUO rats].
OBJECTIVE
To observe the expression and co-locolization of tissue transglutaminase (tTG) and connective tissue growth factor (CTGF) in kidneys from rats with tubulointerstitial fibrosis.


METHODS
The animal models of unilateral ureteral obstruction (UUO) were used. The rats were randomly divided into the sham-operation group (n=5), the UUO group (n=6), and the Enalapril-treated UUO group (n=6). All the rats were sacrificed on day 9, the kidneys were collected, and renal interstitial fibrosis was examined by periodic acid-Schiff (PAS) staining. The expression and localization of tTG, CTGF, and Fibronectin( FN) in the obstructed kidneys were detected by immunohistochemistry staining. The protein levels of tTG and CTGF of the whole kidney homogenates were determined by Western blot analysis.


RESULTS
Weak signals of tTG, CTGF, and FN-positive immunostaining were observed in renal tubular cells and tubulointerstitium, and very rare positive signals were seen in the glomeruli in the sham-operation group. However, much intensive signals of tTG, CTGF, and FN-positive immunostaining were observed in renal tubular cells and tubulointerstitium in the UUO group, and the intensity of signals were decreased in the Enalapril-treated UUO group. Co-localization of tTG and CTGF immunoreactivity were observed in tubulointerstitium in the UUO group. The levels of tTG and CTGF protein analyzed by Western blotting were increased remarkably in the UUO group compared with the sham-operation group, and a significant reduction of tTG and CTGF protein levels were presented in the Enalapril-treated UUO group compared with the UUO group. The levels of tTG protein had positive correlation with the levels of CTGF protein (r=0.683, P<0.05), and with the semi-quantitative levels of FN expression (r=0.737, P<0.05).


CONCLUSIONS
Both tTG and CTGF may play a concordant role in the pathogenesis of renal tubulointerstitial fibrosis,and Enalapril may suppress the development of fibrosis partially via down-regulation of tTG and CTGF expression.
Chen
Dong
D
Department of Nephrology, Peking University First Hospital, Beijing 100034, China.
Huang
Hai-chang
HC
Yu
Lu
L
D000818:Animals; D055513:Connective Tissue Growth Factor; D005353:Fibronectins / Q000096:biosynthesis; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011503:Transglutaminases / Q000096:biosynthesis*; D014517:Ureteral Obstruction / Q000150:complications
C526316:CCN2 protein, rat; D005353:Fibronectins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor; D011503:Transglutaminases