Growth factor expression in the obstructed developing and mature rat kidney

The purpose of this study is to evaluate the role of keratinocyte growth fa ctor (KGF), transforming growth factor-alpha (TGF-alpha), and their recepto rs in altered renal growth caused by complete ureteral obstruction in the d eveloping kidney. Neonatal and adult rats underwent complete unilateral ure teral ligation or sham operation. The kidneys were harvested at 1, 5, 10, 2 0, and 30 days after obstruction. Renal growth and development was assessed by histology and immunohistocytochemical localization of vimentin, cytoker atin and smooth muscle-or actin, Cellular proliferation was measured by [H- 3]thymidine labeling index of all cells. RNase protection assays were used to quantify mRNA encoding for KGF, KGF receptor, TGF-alpha, and epidermal g rowth factor (EGF) receptor. Ureteral obstruction in the developing kidneys resulted in decreased DNA synthesis, rapid parenchymal loss, myofibroblast proliferation in the interstitium, decreased tubular epithelial cells form ation, and development of cystic dysplasia. In comparison, obstruction in t he mature kidneys resulted in transient growth in the medullary ductal cell s, parenchymal loss, and myofibroblast proliferation at a later time, lymph ocytic infiltration in the interstitium but not cystic dysplasia. KGF and K GF receptor mRNA levels were increased in obstructed neonatal kidneys. Simi larly, TGF-alpha and EGF receptor mRNA levels were increased. Delayed and m ore moderate increases in KGF, KGF receptor, and TGF-alpha expression were also seen in the obstructed mature kidneys. Of importance, the amount of EG F receptor mRNA was not increased in the obstructed compared with the contr alateral or sham-operated adult kidneys. This study suggests that obstructi on alters the normal expression pattern of KGF, TGF-alpha, and their recept ors in renal development. These changes may be responsible for the impaired renal growth and altered development seen in ureteral obstruction of the k idneys. Although some changes are similar to those seen in the adult kidney , the increased expression of TGF-alpha and cystic dysplasia are unique to neonatal obstruction.