GENE-EXPRESSION AFTER UNINEPHRECTOMY IN THE RAT - SIMULTANEOUS EXPRESSION OF POSITIVE AND NEGATIVE GROWTH-CONTROL ELEMENTS

Purpose: Compensatory renal growth after contralateral nephrectomy consists largely of hypertrophy of the renal cortex. The signals initiating compensatory renal growth are as yet unknown. Materials and Methods: Using a technique of quantitative dot-blot hybridization, we examined the expression of a number of genes after contralateral nephrectomy in the rat in an effort to establish a characteristic ''fingerprint'' which might shed light on the mechanism of compensatory renal growth. Results: Negative growth control elements, including transcriptional repressors (WT-1, junB, myn, HNF-1, p53, RB, Dr1, gas2, gadd153) were induced 1.7 to 4.7-fold within 1 hour after uninephrectomy, as were positive growth control elements (egr-1, c-jun, cyclin C, cyclin E; 1.0- to 4.2-fold induction). The steady state mRNA levels for heat shock genes hsp70, hsp86 and hsp90 beta, as well as extracellular matrix genes fibronectin and collagen I (alpha(1) chain) were also increased 1 hour after uninephrectomy. In addition, 2 Na+-specific exchangers (NHE-1 and Na/Ca) were induced within 1 hour after uninephrectomy. Conclusions: These results suggest the coordinate expression of positive and negative growth control elements early in this physiologic model of organ growth.