Regulation of gene expression in renal compensatory growth

Compensatory renal hypertrophy is characterized by an increase in cell protein content. There are a number of different cellular mechanisms by which such an increase could be mediated. The relative contributions of transcriptional and posttranscriptional regulation of gene expression to the increase in constitutively expressed cellular proteins were examined in mouse kidneys undergoing compensatory growth following unilateral nephrectomy (UNI-NX). Over the 14-day study period, total protein per kidney increased by up to 37%. Northern blot analysis of the expression of the mRNAs for a number of genes associated with cell growth indicated that there was no significant increase in steady-state levels of these selected genes in nephrectomized compared with sham-operated animals. In vitro assays to measure transcriptional regulation of the same set of genes in compensatory growth showed no increase in the rate of transcription. However, transcription of the 18S ribosomal RNA gene was increased 24 hours after nephrectomy. Immunoblots of two representative proteins showed that the concentration of these proteins in total kidney protein remained constant in the different experimental groups. Since total protein increased, the concentration of these proteins in the hypertrophied kidney must have increased. Taken together, these data suggest that posttranscriptional mechanisms may account for the increase in at least some constitutively expressed proteins in cells undergoing compensatory growth.