Temporal changes in insulin-like growth factor I, c-fos, and c-jun gene expression during hyperplastic kidney growth in weanling rats.

Abstract

We have previously determined that compensatory renal growth (CRG) during the initial 24-48 h after uninephrectomy (UNX) is GH independent in weanling animals, but associated with significant increases in insulin-like growth factor I (IGF-I) and IGF-I receptor gene expression. The purpose of the present study was to determine the temporal sequence of molecular and cellular events that occur at various time points (1, 6, 12, 18, 24, 48, and 72 h post-UNX) during this early period of accelerated renal growth in the weanling (21- to 25-day-old) rat. Rapid and sustained increases in steady state renal IGF-I receptor and IGF-I messenger RNA (mRNA) were observed at 1 and 6 h, respectively, and remained elevated in the remnant kidneys until 72 h post-UNX. The mRNAs for the early response genes, c-fos and c-jun, were not induced in the remnant kidneys from weanling rats until between 12-18 h, but were also sustained through 48 h post-UNX. Increases in remnant kidney DNA content and [3H]thymidine incorporation also occurred from 18-48 h post-UNX and returned to baseline levels by 72 h post-UNX, indicating that the hyperplastic response in the weanling remnant kidney occurs over a discrete period early after UNX. Neither IGF-I nor early response genes were elevated in kidneys from adult animals, which exhibited only hypertrophic renal growth at those early time points after UNX. These findings suggest that early CRG in the weanling rat is associated with rapid increases in IGF-I mRNA followed by a rise in c-fos and c-jun gene expression and a mitogenic response. Furthermore, when the mRNA levels of IGF-I and early response genes returned to baseline levels, mitogenic growth stopped, and slower prolonged hypertrophic renal growth ensued.