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

Abstract

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.