The expression of epidermal growth factor and transforming growth factor-beta1 in the stenotic tissue of congenital pelvi-ureteric junction obstruction in children.

PURPOSE

The aim of this study was to test the hypothesis that expression of epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGF-beta 1) may be altered in stenotic tissue of patients with congenital hydronephrosis caused by pelviureteric junction (PUJ) obstruction and to evaluate the role of these 2 growth factors.

METHODS

The expression of EGF and TGF-beta 1 was evaluated in tissue specimens in 25 children with PUJ obstruction and 15 controls with normal PUJs by immunohistochemistry, in situ hybridization, and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. All the signals of mRNA products were normalized to the mRNA levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) a housekeeping gene, as a ratio.

RESULTS

On RT-PCR study, the amount of TGF-beta 1 mRNA in stenotic tissue was higher than in controls, in addition, EGF gene expression in the obstructed junction was significantly lower than in normal junctions. The TGF-beta 1 to GAPDH ratio was 0.57 +/- 0.26 and 0.36 +/- 0.19 in the stenotic tissue and the normal ureter, respectively (P =.012). The EGF to GAPDH ratio was 0.17 +/- 0.08 and 0.37 +/- 0.14 in the stenotic tissue and the normal ureter, respectively (P =.0001). Furthermore, the positive correlations were found between TGF-beta1 gene and protein expression (r = 0.601; P =.001), TGF-beta 1 gene and drainage clearance half-time (T1/2) (r = 0.474; P =.017), TGF-beta 1 protein expression, and T1/2 (r = 0.516; P =.008). A negative correlation was found between EGF gene and T1/2 (r = -0.448; P =.025). On immunolabeling and in situ hybridization labeling, the expression of TGF-beta 1 protein was strongly positive and confined to the muscle cells, spindle cells, and collagen fibers in the stenotic tissue; the expression of TGF-beta 1 mRNA was moderately positive and mainly distributed in the collagen of the stenotic segment, both the expression of EGF protein and mRNA were negative in the normal ureter.

CONCLUSIONS

There were increased TGF-beta 1 mRNA expression and decreased EGF mRNA expression in the stenotic tissue after clinical ureteropelvic junction obstruction. The alteration of EGF and TGF-beta 1 expression may be involved in the pathogenesis of congenital hydronephrosis.