Effects of IGFBP-2 overexpression in vitro and in vivo

Insulin-like growth factor-binding proteins (IGFBPs) are important modulato rs of IGF actions and may have both stimulatory and inhibitory effects. Exp ression of IGFBP-2 is increased after fasting and in a variety of pathologi cal conditions. However, the specific role of IGFBP-2 in growth physiology remains to be determined. In this review, we summarize data from in vitro a nd in vivo models suggesting that IGFBP-2 has mainly inhibitory effects on IGF actions. Since the growth hormone (GH)/IGF system is involved in a numb er of pathological alterations of the kidney and these changes may - at lea st in part - be due to increased IGF-I, local overexpression of inhibitory IGFBP-2 in the kidney might prevent IGF-I-induced lesions. This hypothesis will be tested by crossing GH transgenic mice, a common model of glomerulos clerosis, with transgenic mice characterized by systemic and renal overexpr ession of IGFBP-2.