![]() Considering that IGFBP3 plays a role in several different contexts, its expression is regulated by many factors. Aside from its effects on IGF-1/IGF-1R interaction, IGFBP3 also plays a role as growth inhibitor and proapoptotic factor in an IGF-independent manner ( Firth and Baxter, 2002 Longobardi et al., 2003 Takaoka et al., 2006). The status of the GH/IGF axis at birth or in early postnatal life is not predictive of later growth, and therefore hormone measurements in SGA infants or children are not indicated in routine care ( Leger et al., 1996). Most SGA children show catch-up growth during the first 2 yr of life, but ∼15% remain short throughout childhood and adolescence and into adulthood ( Klammt et al., 2008 Labarta et al., 2009). SGA children represent a group of newborns (5–10%) whose birth weight and/or length are less than −2 SD from the mean for gestational age ( Clayton et al., 2007). The growth hormone (GH)/IGF/IGFBP axis has been extensively studied in neonates with intrauterine growth retardation and in children born small for gestational age (SGA). Insulin-like growth factor–binding protein 3 (IGFBP3), the main circulating carrier of insulin-like growth factors (IGFs) in postnatal life, inhibits or enhances the effects of IGFs by modulating the amount of free IGF type 1 (IGF-1), by repressing its transfer from the circulation to tissue sites of action, and by regulating the interaction between IGFs and IGF-1 receptor (IGF-1R) ( Mohan and Baylink, 2002). ![]() Our results shed light on the intricate GH/IGF pathway, suggesting p73 as a good biomarker of the clinical risk for SGA children to remain short in adulthood. ![]() We found that mRNA expression levels of p73 and IGFBP3 are significantly lower in SGA children compared with controls and, in particular, p73 mRNA expression is significantly lower in SGA children with respect to height. As IGFBP3 plays a key role in regulating the growth hormone/insulin-like growth factor type 1 (GH/IGF1) axis, whose alterations in gene expression appear to have a role in the growth failure of children born small for gestational age (SGA), we measured the mRNA expression levels of p73 and IGFBP3 in a group of SGA children. We demonstrate that IGFBP3 is a direct TAp73α (the p73 isoform that contains the trans-activation domain) target gene and activates the expression of IGFBP3 in actively proliferating cells. The principal aim of this study was to investigate whether p73, a member of the p53 gene family, has a role in the regulation of the IGFBP3 expression and whether this regulation occurs in a context of cell survival or death. The regulation of insulin-like growth factor–binding protein 3 (IGFBP3) gene expression is complex, because it can be induced by agents that both stimulate and inhibit the proliferation.
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