Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats

The renal insulin-like growth factor-I (IGF-I) system has been implicated i n the pathogenesis of renal hypertrophy, altered hemodynamics, and extracel lular matrix expansion associated with early diabetes. The relative abundan ce of IGF binding proteins (IGFBPs) in the renal microenvironment may modul ate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not b een characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP-1 to -6 messenger RNAs (mRNAs ) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In contro l, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed w ith a predominance of IGFBP-5, The onset of renal hypertrophy in STZ-induce d diabetes was associated with a rapid and site-specific induction of IGFBP -1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-5, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased i n diabetic glomeruli, cortical, and inner medullary peritubular interstitia l cells at days 3, 7, and 14. Although normal glomeruli failed to express I GFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increase d in cortical tubular cells at each time point tested. Peak induction of IG FBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7 . IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persiste ntly elevated above control. By immunoperoxidase staining, similar alterati ons in the pattern of IGFBP-3 and -5 protein expression were observed at ea ch time point. The preferential and site-specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or pa racrine actions of IGF-I and contribute to the pathogenesis of the early ma nifestations of diabetic nephropathy. (C) 1998 by the National Kidney Found ation, Inc.