TEMPORAL CHANGES IN INSULIN-LIKE GROWTH-FACTOR-I, C-FOS, AND C-JUN GENE-EXPRESSION DURING HYPERPLASTIC KIDNEY GROWTH IN WEANLING RATS

We have previously determined that compensatory renal growth (CRG) dur ing the initial 24-48 h after uninephrectomy (UNX) is GH independent i n weanling animals, but associated with significant increases in insul in-like growth factor I (IGF-I) and IGF-I receptor gene expression. Th e 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 acc elerated renal growth in the weanling (21- to 25-day-old) rat. Rapid a nd sustained increases in steady state renal IGF-I receptor and IGF-I messenger RNA (mRNA) were observed at 1 and 6 h, respectively, and rem ained elevated in the remnant kidneys until 72 h post-UNX. The mRNAs f or the early response genes, c-ibs and c-jun, were not induced in the remnant kidneys from weanling rats until between 12-18 h, but were als o sustained through 48 h post-UNX. Increases in remnant kidney DNA con tent and [H-3]thymidine incorporation also occurred from 18-48 h post- UNX and returned to baseline levels by 72 h post-UNX, indicating that the hy perplastic response in the weanling remnant kidney occurs over a discrete period early after UNX. Neither IGF-I nor early response ge nes 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 g ene expression and a mitogenic response. Furthermore, when the mRNA le vels of IGF-I and early response genes returned to baseline levels, mi togenic growth stopped, and slower prolonged hy pertrophic renal growt h ensued.