Expression of the Wnt gene family during late nephrogenesis and complete ureteral obstruction

Because the Wnt-4, -7b, and -11 genes are expressed in metanephric kidneys and code for secreted glycoproteins that may serve as mediators of the tran sformation of: renal mesenchyme to epithelium, we investigated the pattern of Wnt gene expression in late metanephrogenesis and after ureteral obstruc tion. Newborn and 10-, 20-, and 60-day-old rats underwent complete unilater al ureteral ligation or sham operation. The kidneys were collected bilatera lly 1, 5, 10, 20, or 30 days later. RNase protection assays were used to qu antify the amounts of mRNA encoding Wnt-4, -7b, and -11, E-cadherin, and cy tokeratin-19. Renal development was assessed by histologic characterization of vimentin, cytokeratin, E-cadherin, and beta-catenin distribution. Durin g normal development, the amounts of mRNA encoding Wnt-4 and Wnt-11 increas ed during gestation and then abruptly decreased after the completion of met anephrogenesis, 15 days after birth. In contrast, the amounts of mRNA encod ing Wnt-7b, E-cadherin, and cytokeratin-19 increased during development and into adulthood. In neonatally obstructed kidneys, the expression of Wnt-4 was abnormally maintained when obstruction was induced before the completio n of renal development and was reactivated when obstruction was induced aft er the completion of metanephrogenesis. Wnt-7b expression was minimally aff ected and Wnt-11 expression was only transiently affected by obstruction. I n neonatally obstructed kidneys, the differentiation of mesenchyme to epith elium failed to proceed normally, with the majority of cells maintaining vi mentin expression and some differentiated epithelial cells reverting to vim entin expression. In addition, the expression of E-cadherin and cytokeratin was increased in epithelial cells. Changes in the expression of Wnt genes were correlated with histologic changes. This study suggests that Wnt-4 and -11 are likely to be important mediators of the transformation of mesenchy me to epithelium in the kidney. Obstruction induced during metanephrogenesi s disrupts the normal pattern of Wnt-4, -7b, and -11 expression and interfe res with the normal transformation process in developing kidneys, by mainta ining the mesenchymal component and inducing the transformation of epitheli um to mesenchyme.