Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: Direct correlation with clinical retinopathy of prematurity

Hellström, Ann; Perruzzi, Carole; Ju, Meihua; Engström, Eva; Hård, Anna‐Lena; Liu, Jun Li; Albertsson‐Wikland, Kerstin; Carlsson, Björn; Niklasson, Aimon; Sjödell, Lena; LeRoith, Derek; Senger, Donald R.; Smith, Lois E H

doi:10.1073/pnas.101113998

Cited by 523 publications

(424 citation statements)

References 38 publications

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“…Our observations showing decreased levels of Foxf1 and Foxf2 mRNA in Lif, Igf-I, and Lif/Igf-I knockouts would support alterations in mesenchymal and vasculogenesis maturation mediated by IGF-I and LIF. Although LIF function in vasculogenesis is poorly known, these results are consistent with previous reports linking IGF-I and angiogenesis in tissues such as brain and retina (Hellstrom et al, 2001;LopezLopez et al, 2004;Ruberte et al, 2004). Blocking IGF-IR signalling in lung explants, in addition to reduced lung growth and branching of the epithelium, resulted in an inhibition of endothelial cell development (Han et al, 2003).…”

Section: Discussionsupporting

confidence: 89%

Alterations in alveolar epithelium differentiation and vasculogenesis in lungs of LIF/IGF‐I double deficient embryos

Moreno-Barriuso¹,

López-Malpartida²,

Pablo³

et al. 2006

Developmental Dynamics

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Previous studies on double deficient mice for leukemia inhibitory factor (LIF) and insulin-like growth factor I (IGF-I) reported that they died of respiratory failure, with abnormal lung histology and altered expression of pulmonary markers. Here we analyzed prenatal Lif/Igf-I double mutant mouse embryos to characterize LIF and IGF-I cooperative roles in distal lung epithelium and vascular maturation. Lungs of IGF-I-deficient embryos displayed a higher proportion of type II pneumocytes, less differentiated type I pneumocytes, and failure in alveolar capillary remodeling compared to wild type and LIF-deficient mice. Lif/Igf-I double knockout lungs showed aggravated pulmonary hypoplasia, lower airway volume, increased proliferation, and elevated levels of ERK1/2 activation. In addition, their alveoli were collapsed and lined by type II cells. The differentiation of type I cells barely occurred and capillaries remained in the abundant mesenchyme. These results indicate that LIF collaborates with IGF-I in lung alveolar epithelium and vascular maturation.

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Section: Discussionsupporting

confidence: 89%

Alterations in alveolar epithelium differentiation and vasculogenesis in lungs of LIF/IGF‐I double deficient embryos

Moreno-Barriuso¹,

López-Malpartida²,

Pablo³

et al. 2006

Developmental Dynamics

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“…Furthermore, IGF-I and VEGF have an additive effect on the KSIMM proliferation rate, which suggests that these two growth factors may act at least in part independently to promote growth. Vascular endothelial growth factor and IGF-I cellular pathways have been reported to either act independently (Hellstrom et al, 2001) or to interact (Smith et al, 1999) in normal endothelial cells. The relationship between VEGF and IGF-I signalling pathways including those involved in cell survival in KS is the focus of ongoing studies.…”

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival

et al. 2005

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Kaposi's sarcoma (KS) is a highly vascular tumour and is the most common neoplasm associated with human immunodeficiency virus (HIV-1) infection. Growth factors, in particular vascular endothelial growth factor (VEGF), have been shown to play an important role in its development. The role of insulin-like growth factors (IGFs) in the pathophysiology of different tumours led us to evaluate the role of IGF system in KS. The IGF-I receptors (IGF-IR) were identified by immunohistochemistry in biopsies taken from patients with different AIDS/HIV-related KS stages and on KSIMM cells (an established KS-derived cell line). Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3 H-thymidine incorporation of 130±27.6% ( P <0.05) similar to that induced by VEGF and with which it is additive (281±13%) ( P <0.05). Moreover, specific blockade of the receptor (either by α IR3 antibody or by picropodophyllin, a recently described selective IGF-IR tyrosine phosphorylation inhibitor) induced KSIMM apoptosis, suggesting that IGF-IR agonists (IGF-I and -II) mediate antiapoptotic signals for these cells. We were able to identify an autocrine loop essential for KSIMM cell survival in which IGF-II is the IGF-IR agonist secreted by the cells. In conclusion, IGF-I pathway inhibition is a promising therapeutical approach for KS tumours.

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“…This phase is characterized by hypoxia-induced retinal neovascularization similar to that observed in other proliferative retinopathies. 11 Currently, if preterm infants at potential risk of developing severe ROP were early identified, they could receive an even more careful and individual perinatal care concerning their various risk factors. This approach would facilitate planning the best moment to introduce eye examination, because sicker children, as well as those with a worse postnatal prognosis, are at greater risk for the onset of ROP.…”

Section: Discussionmentioning

confidence: 99%

A predictive score for retinopathy of prematurity in very low birth weight preterm infants

Eckert

Filho

Maia

et al. 2011

Eye

101

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Aims This study describes the development of a score based on cumulative risk factors for the prediction of severe retinopathy of prematurity (ROP) comparing the performance of the score against the birth weight (BW) and gestational age (GA) in order to predict the onset of ROP. Methods A prospective cohort of preterm infants with BWp1500 g and/or GAp32 weeks was studied. The score was developed based on BW, GA, proportional weight gain from birth to the 6th week of life, use of oxygen in mechanical ventilation, and need for blood transfusions from birth to the 6th week of life. The score was established after linear regression, considering the impact of each variable on the occurrences of any stage and severe ROP. Receiver operating characteristic (ROC) curves were used to determine the best sensitivity and specificity values for the score. All variables were entered into an Excel spreadsheet (Microsoft) for practical use by ophthalmologists during screening sessions. Results The sample included 474 patients. The area under the ROC curve for the score was 0.77 and 0.88 to predict any stage and severe ROP, respectively. These values were significantly higher for the score than for BW (0.71) and GA (0.69) when measured separately. Conclusions ROPScore is an excellent index of neonatal risk factors for ROP, which is easy to record and more accurate than BW and GA to predict any stage ROP or severe ROP in preterm infants. The scoring system is simple enough to be routinely used by ophthalmologists during screening examination for detection of ROP.

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Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: Direct correlation with clinical retinopathy of prematurity

Cited by 523 publications

References 38 publications

Alterations in alveolar epithelium differentiation and vasculogenesis in lungs of LIF/IGF‐I double deficient embryos

Alterations in alveolar epithelium differentiation and vasculogenesis in lungs of LIF/IGF‐I double deficient embryos

Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival

A predictive score for retinopathy of prematurity in very low birth weight preterm infants

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