DIFFERENTIAL MESSENGER-RNA EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR SYSTEM DURING RENAL INJURY AND HYPERTROPHY

The cellular effects of insulin-like growth factor I (IGF-I) are modif ied by a family of binding proteins (IGFBPs) that act as reservoirs in serum for the growth factor and are produced locally by tissues, incl uding the kidney. Because regulation of these proteins may influence r enal repair, either directly or by their interactions with IGF-I, we s tudied gene expression during the recovery from renal failure induced by folic acid and during the compensatory increase in renal function f ollowing uninephrectomy (UNX). Expression of IGF-I, the IGF-I receptor (IGF-IR), and all six IGFBPs was detected using an ribonuclease prote ction assay. IGFBP-5 was the most abundant binding protein mRNA presen t in kidney, whereas IGFBP-2 and -6 were the least abundant. During re generation following folic acid-induced acute renal failure, IGF-I, IG FBP-3, and IGFBP-5 mRNAs declined in abundance approximately two- to t hreefold. On the other hand, IGF-IR, IGFBP-1, and IGFBP-2 were increas ed (similar to 2-, 6-, and 6-fold, respectively) in the first 24 h. IG FBP-1 mRNA remained elevated for at least 3 days. Despite the known in crease in cellular RNA content following UNX, little difference in spe cific expression of mRNAs was observed. Because IGFBP-1 has been shown to stimulate cell migration and has previously been localized to the distal nephron, the site of greatest injury in the folic acid model, t hese data are compatible with the notion that this protein may functio n either directly to affect cellular repair or act as a reservoir for IGF-I under conditions of cellular damage.