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Abstract Introduction: Any type of nutritional imbalance experienced during childhood will affect the health of an individual, both in their childhood and their adulthood. Several studies have proved that there is an association between cardiovascular disease (CVD) risk and endocrine and lipid markers at early stages of life. Objective: To establish the relationship between nutritional status (IGF-1 and serum levels of its binding proteins IGFBP-1, IGFBP-2 and IGFBP-3), and CVD risk markers in students aged 7 to 9 years. Materials and methods: Cross-sectional observational study conducted in 84 children attending two schools from Bogotá D.C. and Soacha, Colombia, to identify the relationship between possible variations in CVD risk markers and nutritional status. Sexual development stage, lipid profile, anthropometric data, blood sugar levels and IGF-1 and IGFBP serum levels of all participants were measured. Statistical analysis was conducted using the Pearson's correlation coefficient, the analysis of variance (ANOVA), and the Kruskall-Wallis, Games-Howell and Dunnett's tests. The confidence interval and statistical significance were 95% and p<0.05, respectively. Results: IGFBP-1 and IGFBP-2 levels proportionally decreased as weight increased. An inverse correlation between both proteins and triglyceride levels was found, as well as a direct correlation with HDL cholesterol levels. Conclusions: Alterations in CVD risk markers can be identified during childhood. If said alterations are timely detected, it is possible to adopt preventive and therapeutic actions such as the promotion of public policies aimed at preventing childhood overweight and obesity, which in turn will reduce the risk of developing cardiovascular disease in adulthood.
Resumen Introducción. Los desequilibrios nutricionales en la infancia afectan la salud tanto en la niñez como en la adultez. Estudios previos demuestran la asociación de marcadores endocrinos y lipídicos con riesgo cardiovascular (RCV) desde edades tempranas. Objetivo. Establecer la relación entre estado nutricional (niveles séricos de IGF-1 y sus proteínas enlazantes IGFBP-1, IGFBP-2 e IGFBP-3) y marcadores de RCV en estudiantes de 7 a 9 años. Materiales y métodos. Estudio observacional comparativo transversal realizado en 84 niños de 2 colegios de Bogotá D.C. y Soacha, Colombia, para identificar la relación entre posibles variaciones de marcadores de RCV y estado nutricional. Se midieron los niveles de glucemia y niveles séricos de IGF-1 e IGFBP, el nivel de desarrollo sexual, el perfil lipídico y los valores antropométricos. Para el análisis estadístico se utilizaron el coeficiente de correlación de Pearson, un análisis de varianza (ANOVA) y las pruebas de Kruskal Wallis, Games-Howell y Dunnett. El intervalo de confianza fue del 95% y la significancia estadística, de p<0.05. Resultados. La reducción en los niveles de IGFB-1 e IGFBP-2 fue directamente proporcional al aumento de peso. Por otra parte, se observó una correlación inversa entre ambas proteínas y concentraciones de triglicéridos, y una directa con los niveles colesterol HDL. Conclusiones. Las alteraciones de marcadores de RCV se pueden identificar en la infancia. Si estas son detectadas a tiempo es posible adoptar medidas preventivas y terapéuticas como la promoción de políticas públicas dirigidas prevenir el sobrepeso infantil, lo que a su vez reducirá el riesgo de padecer enfermedades cardiovasculares en edades adultas.
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Insulin-like growth factor binding proteins (IGFBPs) are major regulators of insulin-like growth factor bioavailability and activity in metabolic signaling. Seven IGFBP family isoforms have been identified. Recent studies have shown that IGFBPs play a pivotal role in metabolic signaling and disease, including the pathogenesis of obesity, diabetes, and cancer. Although many studies have documented the various roles played by IGFBPs, transcriptional regulation of IGFBPs is not well understood. In this review, we focus on the regulatory mechanisms of IGFBP gene expression, and we summarize the findings of transcription factor activity in the IGFBP promoter region.
Subject(s)
Humans , Biological Availability , Gene Expression , Insulin-Like Growth Factor Binding Protein 2 , Insulin-Like Growth Factor Binding Proteins , Liver , Metabolic Diseases , Obesity , Promoter Regions, Genetic , Protein Isoforms , Transcription FactorsABSTRACT
Abstract Introduction: Nutritional vulnerability is more evident during childhood, since malnutrition has an impact on academic performance and is linked to different diseases during this period. Likewise, an increase in the incidence and prevalence of obesity in children has been observed, therefore, researches that assess nutritional conditions of children attending schools may have high-impact results in terms of public health. Objective: To relate children's nutritional condition by using anthropometry, with serum concentrations of insulin-like growth factor 1 (IGF-1) and its binding protein 2 (IGFBP-2). Materials and methods: A cross -sectional observational and comparative study was performed in children aged 7 to 9 attending two schools, one from the public sector and the other from the private sector. An anthropometric assessment was performed in 157 children, while IGF-1 and IGFBP (enzyme immunoassay) serum concentrations were measured in 81 children. Pearson's coefficient, analysis of variance (ANOVA), Dunnet's test and Games Howell's test, with a 95% confidence interval and a p<0.05 statistical significance, were considered for performing the statistical analysis. Results: Overweight and obesity were found in 46 subjects; the prevalence of obesity was higher in boys, while overweight prevalence was higher in girls. A direct relation between IGF-1 and height (p<0,05) was observed, while an inverse relation between IGFBP-2 and BMI (p<0,001) was found. Conclusions: IGF-1 serum concentrations were higher in students attending the public school.
Resumen Introducción. Una de las etapas con mayor vulnerabilidad del estado nutricional es la infancia, pues en este periodo la desnutrición interfiere con el desempeño escolar y se asocia a enfermedades; asimismo, se ha observado aumento de la incidencia y prevalencia de obesidad en niños, por lo que investigaciones de evaluación nutricional en población escolar pueden tener alto impacto en salud pública. Objetivo. Relacionar el estado nutricional -antropometría- con niveles séricos del factor de crecimiento similares a la insulina 1 (IGF-1) y su proteína enlazante 2 (IGFBP-2). Materiales y métodos. Estudio observacional de corte transversal comparativo entre estudiantes de 7 a 9 años de dos colegios, uno público y otro privado, mediante el cual se realizó valoración antropométrica de 157 niños y medición de niveles séricos de IGF-1 e IGFBP-2 (enzimoinmunoanálisis) en 81 niños. Para el análisis estadístico se tuvo en cuenta coeficiente de Pearson, análisis de varianza (ANOVA), test de Dunnet y Games Howell, intervalo de confianza del 95% y significancia estadística de p<0.05. Resultados. Se registró sobrepeso y obesidad en 46 sujetos; la obesidad fue más prevalente en niños mientras que el sobrepeso en niñas. Se encontró relación directa entre IGF-1 y talla (p<0.05) y relación inversa entre IGFBP-2 e IMC (p<0.001). Conclusiones. Las concentraciones séricas de IGF-1 fueron mayores en la institución pública.
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This study was conducted to determine if the main components of the somatotropic axis change during the early phase of pregnancy in the maternal blood system and whether differences exist on day 18 after pregnancy recognition by the maternal organism. Blood samples of pregnant heifers (Holstein Friesian; n = 10 after embryo transfer) were obtained on the day of ovulation (day 0), as well as on days 7, 14, 16 and 18 and during pregnant, non-pregnant and negative control cycles. The oncentrations of progesterone (P4), oestrogen, growth hormone (GH), insulin-like growth factor-1 and -2 (IGF1, -2) and IGF-binding protein-2, -3 and -4 (IGFBP2, -3, -4) were measured. The mRNA expressions of growth hormone receptor 1A, IGF1, IGF2, IGFBP2, IGFBP3 and IGFBP4 were detected using RT-qPCR in liver biopsy specimens (day 18). In all groups, total serum IGF1 decreased from day 0 to 16. Notably, IGFBP4 maternal blood concentrations were lower during pregnancy than during non-pregnant cycles and synchronized control cycles. It can be speculated that the lower IGFBP4 in maternal blood may result in an increase of free IGF1 for local action. Further studies regarding IGFBP4 concentration and healthy early pregnancy are warranted.
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Female , Pregnancy , Axis, Cervical Vertebra , Biopsy , Embryonic Structures , Growth Hormone , Liver , Ovulation , Progesterone , Receptors, Somatotropin , RNA, MessengerABSTRACT
Objective To investigate the role of Annexin A7CANXA7) in the development of HCC by analyzing ANXA7 expression in hepatocarcinogenesis and identifying its potential interaction molecule. Methods ANXA7 mRNA expression was analyzed by real-time PCR in 48 HCC tissues and tumor adjacent tissues, and different hepatic cancer tissues and cell lines. To analyze the effect of ANXA7 on hepatoma proliferation, ANXA7 was overexpressed or inhibited by specific siRNA in hepatic cancer cells. Co-immunopricipitation (co-IP) method was used to detect the specific binding protein of ANXA7 in HCC cells. The key sites of protein interaction were analyzed by point mutation. Western blotting analysis was used to study the effect of ANXA7 on IGFBP2 activated ERK1/2 phosphorylation. Results The expression of ANXA7 was down-regulated in both hepatoma tissue samples and hepatoma cell lines. Insulin-like growth factors binding protein 2 (IGFBP2) could specifically bind with ANXA7 through the key ROD site. Up-regulated expression of ANXA7 could inhibit the proliferation of tumor cells (P
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As a high sensitive biomarker of lung cancer ,IGFBP2 plays an important role in the occur-rence,development and treatment of lung cancer .Studies have showed that it promotes tumor progression by acti-vating the IGF1R and integrin mediated signal transduction pathway .Recent researches have demonstrated that it participates in targeted therapy of lung cancer ,which may become a new target for the treatment of lung cancer . This paper makes a review on the relationship between IGFBP 2 and lung cancer .
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Objective To establish a zebrafish IGFBP-2 gene knock-down model by morphilino modified antisense oligonucleotide injection, so as to investigate the abnormal phenotypes of heart and vessels in early stage of zebrafish development and the expression of zebrafish cardiogenesis related genes. Methods The spatiotemporal expression of IGFBP-2 gene in early stage of zebrafish development was testified by whole mount in situ hybridization with antisense RNA IGFBP-2 probe. The IGFBP-2 morpholino (IGFBP-2 MO) that especially inhibited the gene promoter and standard control morpholino (Con-MO) were designed and synthesized by Gene-tools Corporation. Four different concentration gradients (0.05, 0.10, 0.25 and 1.0 mmol/L) were set as IGFBP-MO injection groups with 0.25 mmol/L Con-MO injection group and wild type group as controls. Contribution to the incidence of heart abnormal phenotypes and mortality rate induced by 4 different IGFBP-2 concentrations injection group was recorded and compared with 2 control groups. Heart abnormal phenotypes at different developmental stages in 0.25 mmol/L IGFBP-2 injection group were observed in detail. To validate the effectiveness of IGFBP-2 MO, the expression of enhanced green fluorescence presented by wild type zebrafish embryos at 12hpf which received single injection of IGFBP-2 EGFP recombinant plasmid and those co-injected with Con-MO or IGFBP-2 MO were detected. To investigate the regulation relationship between IGFBP-2 gene and other cardiogenesis related genes, expression of atrium specific marker gene Amhc was detected in IGFBP-2 MO and wild type group by in situ hybridization. Ventricle specific green fluorescence of Vmhc-EGFP transgenic zebrafish embryos whose IGFBP-2 gene was knocked-down were compared with those untreated. Zebrafish peripheral vascular development in the IGFBP-2 MO group was also checked out by micro-angiography. Results Whole mount in situ hybridization revealed that IGFBP-2 gene expressed in turn at eyes, midbrain and then focused on liver in early stage of zebrafish development. The micro-injection of 0.25 mmol/L IGFBP-2 MO resulted in heart malformation in nearly 60% of all injected zebrafish embryos. Heart malformation phenotypes included slow heart beat, pericardial edema, weak ventricle systole contraction and heart tube looping disorder. Some of them represented atria dilation, blood regurgitation and ciculation obstruction. Wild type zebrafish embryos that received single injection of IGFBP-2 EGFP plasmid DNA or co-injected with Con-MO presented strong enhanced green fluorescence at 12hpf, meanwhile, the fluorescence was barely seen in the embryos co-injected with IGFBP-2 MO. This strongly validated the gene specific knock-down effect of IGFBP-2 MO. Amhc was down-regulated at 48hpf in IGFBP-2 MO group. Vmhc-EGFP transgenic zebrafish down-regulated by IGFBP-2 gene also resulted in attenuated expression of ventriclar-specific green fluorescence protein at 48hpf. Intersegmental blood vessels of IGFBP-2 MO group by micro-angiography at 60hpf demonstrated an sparsate and chaos image, which suggested that IGFBP-2 gene expression was involved in the regulation of normal vascular development. Conclusions Micro-injection of IGFBP-2 MO is an efficient way to knock-down IGFBP-2 gene in zebrafish embryos. IGFBP-2 gene expression down-regulation leads to heart and vessels maldevelopment and have an impact on the expression of cardiogenesis related genes of zebrafish embryos as well. In short, IGFBP-2 plays a critical role in the normal cardiovascular development of zebrafish embryos.
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@#Objective To determine the levels of insulin-like growth factor binding protein-2 (IGFBP-2) in glioma tumor tissue and their clinical significance. Methods The levels of IGFBP-2 in glioma samples from 45 patients were detected with immunohistochemistry. Their correlation with tumor grade, p53 and Ki67 expression levels and the outcome of patients were tested. Results IGFBP-2 increased in glioma tissue in a grade-dependent manner, and significantly correlated with p53 and Ki67 expression. High IGFBP-2 level is significantly associated with earlier tumor recurrence and shorter overall survival. Conclusion Tumor IGFBP-2 levels can supply more prognostic information to the tumor grading system.
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PURPOSE: We performed this study to evaluate the mean serum levels of insulin-like growth factor (IGF)-I, insulin-like growth factor binding protein(IGFBP)-2 and IGFBP-3 in healthy Korean children according to age and sex. METHODS: Ninety two healthy children, consisting of 42 boys and 50 girls, were classified into five groups according to age:neonate; infancy; early childhood; late childhood; and adolescence. We measured serum levels of IGF-I, IGFBP-2 and IGFBP-3 by enzyme-linked immunosorbent assay(ELISA) and analysed the serum levels according to sex and age group. RESULTS: For boys, the mean serum levels of IGF-I(ng/mL) in neonate, infancy, early childhood, late childhood and adolescence were 41.1+/-3.6, 70.9+/-33.7, 103.5+/-97.2, 89.8+/-46.5 and 51.4+/-27.8, respectively. Those of IGFBP-2(ng/mL) were 8.2+/-3.4, 5.8+/-0.4, 9.3+/-4.0, 9.5+/-1.1 and 7.0+/-0.5, respectively. Those of IGFBP-3(ng/mL) were 559.2+/-215.2, 1,333.3+/-692.5, 2,254.6+/-1,513.8, 2,447.1+/-1,464.2, 1,533.6+/-807.4, respectively. For girls, the mean serum levels of IGF-I(ng/mL) according to five age groups were 53.3+/-9.5, 99.3+/-45.8, 69.6+/-51.1, 106.2+/-67.0 and 145.1+/-127.8, respectively. Those of IGFBP-2 (ng/mL) were 9.1+/-7.4, 5.3+/-0.9, 6.9+/-2.0, 10.5+/-3.0 and 7.9+/-1.3, respectively. Those of IGFBP-3(ng/ mL) were 858.2+/-433.4, 1,834.8+/-851.3, 1,404.3+/-570.2, 2,203.5+/-899.4 and 2,029.3+/-1,316.7, respectively. There were significant positive correlations observed between IGF-I and IGFBP-3 levels(r=0.589, P= 0.000). CONCLUSION: IGF-I and IGFBP-3 levels increased as children get older. The peak level of IGFBP-3 was observed in late childhood for both boys and girls, suggesting a current trend of children reaching peak growth velocity before adolescence. The IGFBP-2 level was higher in neonates compare to infancy, suggesting that IGFBP-2 is an important substance for fetal growth.
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Adolescent , Child , Female , Humans , Infant, Newborn , Fetal Development , Insulin-Like Growth Factor Binding Protein 2 , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor IABSTRACT
0.05 ); the positive percentage of IGFBP-2 was statistically higher in breast cancer with metastasis in lymph node than those without metastasis in lymph node (P 0.05 ,r_s= 0.271 ). CONCLUSION: The expression of IGFBP-2 may play an important role in the progression, invasion and metastasis of breast cancer, and there is a positive correlation between the expression of IGFBP-2 and ER in breast cancer. It demonstrates that over expression of IGFBP-2 may be a reference to evaluate unfavourable prognosis of breast cancer.
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Objective To explore the influence of retinoic acid (RA) on the expressions of insulin-like growth factor (IGF)-Ⅱ,type 2 IGF receptor (IGF-2R) and IGF binding protein (IGFBP)-2 mRNA and polypeptides in lungs of hyperoxia-exposed premature rats and its possible molecular mechanism. Methods On the 2nd postnatal day, 260 Sprague-Dawley(SD)preterm rats were randomly divided into 4 groups. Group Ⅰ: air + normal saline (NS) group; Group Ⅱ: hyperoxia(85% O_2) + NS group; Group Ⅲ: air+ RA group; Group Ⅳ: hyperoxia(85% O_2) + RA group. RA was injected to group Ⅲ, Ⅳ intraperitoneally (500 ?g/kg) since the 3rd day after birth, while NS was given to group Ⅰ,Ⅱ daily at the same time as group Ⅲ and Ⅳ. On day 4, 7, 10, 14 and 21 after birth, 8 rats in each group were killed. The mortality of preterm rats was recorded and lung radical alveolar counts (RAC) were examined. The mRNA analysis (RT-PCR) and polypeptides analysis (Western Blot) of IGF-Ⅱ, IGF-2R and IGFBP-2 were performed. Results 1. On the 4～7th day of exposure, the survival rate in all groups were similar. After 7 days of 85% O_2 exposure, the survival rate in group Ⅱ, Ⅳ dropped sharply and there was a significant difference comparing to group Ⅰ, Ⅲ( P