Primary response gene expression in renal hypertrophy and hyperplasia: evidence for different growth initiation processes

Abstract

Unilateral nephrectomy is followed by compensatory renal hypertrophy, a response in which the cells of the contralateral kidney increase in size and protein content without synthesizing DNA or dividing. To determine whether the earliest phase of the hypertrophic response has features similar to mitogenic or differentiation responses, we have characterized the expression of several primary-response genes, the 12-O-tetradecanoylphorbol-13-acetate (TPA)-inducible sequences (TIS) genes, which are rapidly and transiently induced in the absence of intervening protein synthesis, in a variety of mitogenic and differentiation cell systems. TIS gene induction was studied in the contralateral kidney of uninephrectomized and sham-operated mice, as well as in the kidneys of mice in which renal cell proliferation was induced by folic acid injection. Induction of TIS 1, TIS 8, and TIS 11 mRNA levels following folic acid administration peaked at 2 to 4 h and persisted up to 6 to 12 h after mitogenic stimulation. In contrast, a qualitatively different pattern was observed after both uninephrectomy and sham operation; a short-lived increase (up to 1 h) in mRNA levels occurred for the three TIS genes. This pattern was qualitatively similar to that observed in the sham-operated animals. We conclude that renal hypertrophy induced by unilateral nephrectomy is a distinct cellular response, distinguishable at the earliest transcriptional level from a mitogenic response and from the responses that characterize several pathways of cell differentiation.