Genetic ablation of IGFBP-2 suggests functional redundancy in the IGFBP family

Pintar, John E.; Schuller, Alwin G.; Cerro, Joseph A.; Czick, Maureen E.; Grewal, Anoop; Green, Barrett

doi:10.1016/0955-2235(95)00029-1

Cited by 44 publications

(20 citation statements)

References 39 publications

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“…This method, when applied to histomorphometry, has given insight into the developmental role oflGFBPs during foetal ontogene sis [29], Recently, transgenic animals have been used to study the role oflGFBPs. Absence of IGFBP-2 in a trans genic mouse model caused enlarged ventricles and lack of a corpus callosum [30]. This is further evidence of a devel opmental and tissue-specific role for some IGFBPs.…”

Section: Igfbp Determination Methodsmentioning

confidence: 48%

Functional Role of Insulin-Like Growth Factor Binding Proteins

Ranke

Elmlinger

1997

Horm Res

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Insulin-like growth factors (IGF-I, IGF-II) are important regulators of cell division and differentiation. In their free form, IGFs form a complex with specific binding proteins (IGFBPs), six of which have now been characterized. These IGFBPs differ in their ability to bind IGF-I and/or IGF-II, and, depending on their location and metabolic circumstances, they inhibit or augment IGF action to varying extents. New findings have changed our understanding of IGFBPs, which are now considered to be major regulators of IGF action and IGF transport proteins between compartments. Recently, the IGF-inde-pendent action of IGFBPs was discovered. Levels of IGFBP-3, for instance, are important indicators of states of altered growth hormone secretion and action, as well as being important during treatment with growth hormone or IGF-I. IGFBP-1 and -2 levels reflect changes related to nutrition, insulin secretion, foetal development and malignant state. The unravelling of the intricate interactions of IGFs, IGFBPs and their targets is bound to influence our understanding of the physiology and development of biological systems. Likewise, the possibility of regulating the IGFBP system is likely to open up new fields in the treatment of diseases in the future.

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Section: Igfbp Determination Methodsmentioning

confidence: 48%

Functional Role of Insulin-Like Growth Factor Binding Proteins

Ranke

Elmlinger

1997

Horm Res

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“…Knockout mice lacking IGFBP-2 expression did not show overt phenotypic alterations; however, the concomitant upregulation of other IGFBPs and the functional redundancy within this family of related proteins might have hidden the intrinsic effects of IGFBP-2 [49,50,51]. However, there is at least indirect evidence for a role of IGFBP-2 as an inhibitor of IGF actions.…”

Section: Studies Of Igfbp-2 Actions In Animal Modelsmentioning

confidence: 97%

Effects of IGFBP-2 overexpression in vitro and in vivo

Wolf¹,

Lahm²,

Wu³

et al. 2000

Pediatric Nephrology

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Insulin-like growth factor-binding proteins (IGFBPs) are important modulators of IGF actions and may have both stimulatory and inhibitory effects. Expression of IGFBP-2 is increased after fasting and in a variety of pathological conditions. However, the specific role of IGFBP-2 in growth physiology remains to be determined. In this review, we summarize data from in vitro and 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 number of pathological alterations of the kidney and these changes may--at least 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 glomerulosclerosis, with transgenic mice characterized by systemic and renal overexpression of IGFBP-2.

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“…Both IGFBP-2 knockout mice and transgenic mice have been generated (Schneider et al 2000). IGFBP-2 knockout mice exhibited minimal difference, except a decreased spleen size during the early postnatal stages and increased circulating levels of several other IGFBPs in adults (Pintar et al 1995). The IGFBP-2 transgenic mice showed weight reductions in the pancreas, spleen and liver and have been widely used in studies on metabolism (Hoeflich et al 1999;Hedbacker et al 2010).…”

Section: Discussionmentioning

confidence: 98%

Insulin-Like Growth Factor Binding Protein-2 Promotes Adhesion of Endothelial Progenitor Cells to Endothelial Cells via Integrin α5β1

Zhang

Wang

et al. 2015

J Mol Neurosci

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The contribution of endothelial progenitor cells (EPCs) to new vessel formation has been studied in different physiological and pathological conditions for decades. As previously suggested, insulin-like growth factor binding protein-2 (IGFBP-2) may interact with integrins and promote cell migration. However, the role of IGFBP-2 in regulation of EPC functions remains largely unknown. In this present study, we found that overexpression of IGFBP-2 in human umbilical vein endothelial cells (HUVECs) promoted EPC-endothelial adhesion. Conversely, siRNA-mediated depletion of IGFBP-2 inhibited oxygen-glucose deprivation (OGD)-induced EPC-endothelial adhesion. Further, we demonstrated that the arginine-glycine-aspartic acid (RGD) motif in its C-domain is required for interaction with integrin α5β1. In addition, treatment with IGFBP-2 significantly enhanced incorporation of EPCs into tubule networks formed by HUVECs. Thus, our findings suggest that exogenous administration of IGFBP-2 may facilitate neovascularization and improve treatment of ischemic conditions.

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Genetic ablation of IGFBP-2 suggests functional redundancy in the IGFBP family

Cited by 44 publications

References 39 publications

Functional Role of Insulin-Like Growth Factor Binding Proteins

Functional Role of Insulin-Like Growth Factor Binding Proteins

Effects of IGFBP-2 overexpression in vitro and in vivo

Insulin-Like Growth Factor Binding Protein-2 Promotes Adhesion of Endothelial Progenitor Cells to Endothelial Cells via Integrin α5β1

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