Insulin-like growth factor system gene expression in the human kidney.

Abstract

Insulin-like growth factors (IGFs) have significant effects on renal function and have been implicated in renal development and hypertrophy. In order to investigate the renal IGF system in the human, we have used in situ hybridization to map the patterns of gene expression for IGF-I, IGF-II, IGF binding proteins-1 and -2 and both the type-I and type-II IGF receptors in the adult kidney. Since the rat is a model for the study of IGFs in renal physiology and pathophysiology, we compared patterns of IGF gene expression in the rat and human kidney. IGF-I messenger RNA (mRNA) is not detected in the human but is abundant in the rat kidney, while IGF-II is abundant in the human but not detected in the adult rat kidney. IGF-II mRNA is concentrated in renal vascular system, including afferent arterioles and the medullary interstitium. IGF-I and IGF binding protein-1 mRNAs are colocalized in the rat medullary thick ascending limbs of Henle's loops, but neither is detected in the human kidney. IGF binding protein-2 mRNA is concentrated in glomeruli in both species, but, whereas in the human it is expressed in the epithelium of the distal nephron and collecting ducts, in the rat it is localized in the medullary interstitium. The patterns for both type-I and type-II IGF receptor gene expression are identical in both species; however, type-I receptor, mRNA is distinctly more abundant than type-II. Both IGF receptor mRNAs are abundant in the renal tubular epithelium of the medulla and both are barely detectable in proximal tubules. Type I receptor mRNA alone is abundant in glomerular structures. These observations suggest that the autocrine/paracrine roles of IGFs are quite different in rat and human kidney. The conserved patterns of IGF receptor expression, however, suggests that the role of circulating IGFs in regulating renal function may be similar across the species.