miR-17 targets IGF-1 to regulate vascular smooth muscle cell proliferation in coronary artery disease / 西安交通大学学报(医学版)

【Objective】 To investigate the potential mechanism of miR-17 in vascular smooth muscle cells in coronary artery disease (CAD). 【Methods】 mRNA expression of miR-17 and insulin growth factor 1 (IGF-1) in serum and VSMCs of CAD patients were detected by RT-qPCR. Potential targets of miR-17 were detected by bioinformatics and luciferase reporter assay; CCK-8 and cloning formation assay was performed to measure the proliferation of VSMCs. 【Results】 RT-qPCR results showed that compared with those in control group, the miR-17 mRNA expression in VSMCs and serum of CAD patients were significantly upregulated (P<0.01). The results of CCK-8 and clone formation assay showed that compared with those in control group, the number of VSMCs proliferation and cloning formation in the miR-17 overexpression group were significantly increased (P<0.01); those in the miR-17 low expression group were significantly reduced (P<0.01). Bioinformatics analysis showed that the 3’-UTR of IGF-1 had an miR-17 binding site. The luciferase reporter assay showed that the luciferase activity of VSMCs co-transfected with wild-type IGF-1 plasmid and miR-17 mimic was increased (P<0.001). However, the luciferase activity of VSMCs transfected with mutant IGF-1 plasmid and miR-17 mimics remained unchanged. Compared with that in control group, the expression of IGF-1 in VSMCs was upregulated after miR-17 overexpression (P<0.01). And the number of VSMCs proliferation and clone formation in the IGF-1 overexpression group was significantly increased (P<0.05). 【Conclusion】 miR-17 promotes the proliferation of VSMCs by targeting IGF-1. This indicates that miR-17 can be used as a predictive biomarker of CAD, and IGF-1 may be a potential therapeutic target.

The Serum Level of Insulin Growth Factor-1 and Insulin Growth Factor Binding Protein-3 in Children with Henoch-Schönlein Purpura

PURPOSE: We investigated whether serum levels of insulin growth factor-1 (IGF-1) and insulin growth factor binding protein-3 (IGFBP-3) are valuable in predicting clinical outcomes or are correlated with other laboratory findings in children with Henoch-Schönlein purpura (HSP). METHODS: We examined 27 children who were consecutively admitted to our hospital with HSP between January 2011 and February 2012. Blood tests (C-reactive protein, white blood cell count, platelet count, erythrocyte sedimentation rate, albumin, immunoglobulin A, complement C3, antineutrophil cytoplasmic antibody, IGF-1, IGFBP-3) and urine tests were performed upon admission. IGF-1 and IGFBP-3 were resampled in the recovery phase. Controls included 473 children whose IGF-1 and IGFBP-3 were sampled for evaluating their growth, at the outpatient department of pediatric endocrinology in our hospital. IGF-1 and IGFBP-3 were compared between the HSP children and controls, and between the acute and recovery phases in HSP children. The ability of these values to predict clinical outcomes including renal involvement was analyzed using bivariate logistic regression analysis (BLRA). RESULTS: IGF-1 and IGFBP-3 were not different between the HSP children and controls (148.7±117.6 vs. 69.2±96.9, P=0.290: 3465.9±1290.9 vs. 3597.2±1,127.6, P=0.560, respectively). There was no significant difference in IGF-1 or IGFBP-3 between acute and recovery phases. Based on the BLRA, no variable, including IGF-1 and IGFBP-3, could predict clinical outcomes including the presence of nephritis. CONCLUSION: We concluded that IGF-1 and IGFBP-3 do not predict clinical outcomes of HSP, including renal involvement, in this study.

Diagnostic value of growth hormone stimulating test in dwarfism of children and related influencing factors / 国际检验医学杂志

Objective To investigate the diagnostic value of growth hormone(GH) stimulating test in dwarfism of children and related influencing factors .Methods Arginine and L‐dopa were applied to perform GH stimulating test in 642 children with dwarf‐ism .GH levels were detected at 30 ,60 ,90 ,120 ,150 ,180 min after stimulation .All children were divided into GH deficiency (GHD) group ,with peak value of GH less than 10 ng/mL ,and non‐GHD group ,with peak value of GH at least 10 ng/mL .Physical and la‐boratory data of the two groups were compared .Results The proportion of children with GHD and without GHD were 68 .69%and 31 .31% ,respectively ,and with statistical difference(χ2 =6 .19 ,P<0 .05) .The GH peak value ,with a delay ,mainly appeared at 30 and 150 min after stimulation ,accounting for 22 .42% and 34 .27% .Levels of age ,body height standard deviation ,body mass in‐dex ,alanine aminotransferase ,aspartate aminotransferase ,insulin growth factor‐1 and 25‐hydroxyl vitamin D were statistically dif‐ferent between the two groups(P<0 .05) .Conclusion Arginine and L‐dopa combined stimulating test could be used for the diagno‐sis of GHD in children with dwarfism .GH level might be correlated with various physical and laboratory parameters ,which should be considered for the diagnosis of GHD .

Evolution of the biochemical profile of children treated or undergoing treatment for moderate or severe stunting: consequences of metabolic programming? / Evolução do perfil bioquímico de crianças tratadas ou em tratamento para déficit estatural moderado ou grave: consequências da programação metabólica?

OBJECTIVE: to evaluate changes in the biochemical profile of children treated or being treated for moderate or severe stunting in a nutrition recovery and education center. METHODS: this was a retrospective longitudinal study of 263 children treated at this center between August of 2008 to August of 2011, aged 1 to 6 years, diagnosed with moderate (z-score of height-for-age [HAZ] < -2) or severe stunting (HAZ < -3). Data were collected on socioeconomic conditions, dietary habits, and biochemical changes, as well as height according to age. RESULTS: the nutritional intervention showed an increase in HAZ of children with moderate (0.51 ± 0.4, p = 0.001) and severe (0.91 ± 0.7, p = 0.001) stunting during the monitoring. Increased levels of insulin-like growth factor 1 (IGF-1) (initial: 71.7 ng/dL; final: 90.4 ng/dL; p = 0.01) were also observed, as well as a reduction in triglycerides (TG) in both severely (initial: 91.8 mg/dL; final: 79.1 mg/dL; p = 0.01) and in moderately malnourished children (initial: 109.2 mg/dL; final 88.7 mg/dL; p = 0.01), and a significant increase in high-density lipoprotein cholesterol HDL-C only in the third year of intervention (initial: 31.4 mg/dL; final: 42.2 mg/dL). The values of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels remained high throughout the treatment (initial: 165.1 mg/dL; final: 163.5 mg/dL and initial: 109.0 mg/dL; final: 107.3 mg/dL, respectively). CONCLUSION: the nutritional treatment for children with short stature was effective in reducing stunting and improving TG and HDL-C after three years of intervention. However, the levels of LDL-C and TC remained high even in treated children. It is therefore speculated that these changes may result from metabolic programming due to malnutrition. .

OBJETIVO: avaliar as mudanças no perfil bioquímico de crianças tratadas ou em tratamento para déficit estatural moderado ou grave em um centro de recuperação e educação nutricional. MÉTODOS: estudo longitudinal retrospectivo com 263 crianças semi-internas no Centro no período de agosto/2008 a agosto/2011, com idade entre 1 e 6 anos e diagnóstico de déficit estatural moderado, escore-Z da altura-para-idade (AIZ) < -2 e grave (AIZ < -3). Foram coletados dados socioeconômicos, dietéticos e bioquímicos e a evolução estatural segundo a idade. RESULTADOS: com a intervenção nutricional observou-se incremento no escore-z das crianças com déficit estatural moderado (0,51 ± 0,4; p = 0,001) e grave (0,91 ± 0,7; p = 0,001) durante o período de acompanhamento. Observou-se, ainda, aumento nos níveis de fator de crescimento insulina-símile (IGF-1) (inicial: 71,7 ng/dL; final: 90,4 ng/dL; p = 0,01), redução nos triglicérides (TG) tanto nas crianças graves (inicial: 91,8 mg/dL; final: 79,1 mg/dL; p = 0,01) como nas moderadamente desnutridas (109,2 mg/dL para 88,7 mg/dL; p = 0,01) e aumento significativo do lipoproteína de alta densidade (HDL-C) apenas no terceiro ano de intervenção (inicial: 31,4 mg/dL; final: 42,2 mg/dL). Os valores de colesterol total (CT) e lipoproteína de baixa densidade (LDL-C) continuaram elevados durante todo o tratamento (inicial: 165,1 mg/dL; final: 163,5 mg/dL e inicial: 109,0 mg/dL; final: 107,3 mg/dL, respectivamente). CONCLUSÃO: o tratamento nutricional para as crianças de baixa estatura mostrou-se eficaz na redução do déficit estatural e dos TG e melhora dos níveis de HDL-C após três anos de intervenção. Porém, os níveis de LDL-C e CT mostraram-se sempre elevados mesmo nas ...

Insulin Like Growth Factor Binding Protein-5 Regulates Excessive Vascular Smooth Muscle Cell Proliferation in Spontaneously Hypertensive Rats via ERK 1/2 Phosphorylation

Insulin-like growth factor binding proteins (IGFBPs) are important components of insulin growth factor (IGF) signaling pathways. One of the binding proteins, IGFBP-5, enhances the actions of IGF-1, which include the enhanced proliferation of smooth muscle cells. In the present study, we examined the expression and the biological effects of IGFBP-5 in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The levels of IGFBP-5 mRNA and protein were found to be higher in the VSMC from SHR than in those from WKY. Treatment with recombinant IGFBP-5-stimulated VSMC proliferation in WKY to the levels observed in SHR. In the VSMCs of WKY, incubation with angiotensin (Ang) II or IGF-1 dose dependently increased IGFBP-5 protein levels. Transfection with IGFBP-5 siRNA reduced VSMC proliferation in SHR to the levels exhibited in WKY. In addition, recombinant IGFBP-5 significantly up-regulated ERK1/2 phosphorylation in the VSMCs of WKY as much as those of SHR. Concurrent treatment with the MEK1/2 inhibitors, PD98059 or U0126 completely inhibited recombinant IGFBP-5-induced VSMC proliferation in WKY, while concurrent treatment with the phosphatidylinositol-3 kinase inhibitor, LY294002, had no effect. Furthermore, knockdown with IGFBP-5 siRNA inhibited ERK1/2 phosphorylation in VSMC of SHR. These results suggest that IGFBP-5 plays a role in the regulation of VSMC proliferation via ERK1/2 MAPK signaling in hypertensive rats.

Change of serum associated factors in patients with combined pulmonary fibrosis and emphysema / 中国综合临床

Objective To investigate the levels of transformation growth factor-β1 (TGF-β1),vascular endothelial growth factor (VEGF) and insulin growth factor-Ⅰ (IGF-Ⅰ) role in the pathogenesis of serum of patients with combined pulmonary fibrosis and emphysema (CPFE).Methods Recruited 20 patients with CPFE,40 cases with idiopathic pulmonary interstitial fibrosis (IPF) and 40 cases with emphysema who were admitted to our hospital during July 2011 to February 2012.Serum levels of TGF-β1,VEGF and IGF-Ⅰ were detected by ABC-ELISA.Results Serum levels of TGF-β1 and IGF-Ⅰ were significantly higher in patients with CPFE and IPF than these in patients with emphysema (TGF-β1:(160.73 ± 40.62) ng/L vs.(167.35 ± 42.82) ng/L vs.(128.75 ±35.77) ng/L; IGF-Ⅰ:(179.65 ±60.73) ng/L vs.(192.32 ±58.75) ng/L vs.(148.73 ±49.67) ng/L,P ＜ 0.05 or P ＜ 0.01).The IPF group had significantly higher serum level of VEGF than the emphysema group ((506.12 ±82.37) ng/L vs.(437.31 ±62.58) ng/L,P ＜0.01).Serum levels of TGF-β1 and IGF-Ⅰ in CPFE and emphysema groups were positively correlated (r =0.885,0.918 respectively,P ＜ 0.01).Smokers in the CPFE group had significandy lower level of serum VEGF than those who did no smoke ((406.19 ± 66.94) ng/L vs.(482.88 ± 79.91) ng/L,t =-2.287,P =0.035).Conclusion Serum level of VEGF increased significantly in the IPF group,suggesting the participation of VEGF in pulmonary interstitial fibrosis.IGF-Ⅰ involved in the pathogenesis of pulmonary interstitial fibrosis.TGF-β1 and IGF-Ⅰ have a positive linear regressive relationship,which indicates that they may work synergistically in the process of the fibrosis.

Relación del factor de crecimiento insulina tipo I y la malnutrición en pacientes adultos con enfermedad hepática crónica compensada

Los pacientes con hepatopatía crónica presentan malnutrición en grados variables. Uno de los factores implicados en la malnutrición es la deficiencia del factor de crecimiento insulina tipo I. Objetivo: determinar la relación del factor de crecimiento insulina I y la mal nutrición en pacientes con enfermedad hepática crónica compensada. Materiales y métodos: grupo A, formado por 31 pacientes con enfermedad hepática crónica Child Pugh A y grupo B, 16 controles sanos. A los pacientes se les realizó historia clínica, laboratorio, evaluación antropométrica y se determinó el FCI-1 por técnica de inmunoensayo enzimático. Se aplicó T student con el programa computarizado SPSS y un valor de p < 0,05 fue estadísticamente significativo. Resultados: grupo A: 31 pacientes con enfermedad hepática crónica alcohólica y no alcohólica edad entre 40 y 66 años; grupo B: control 16 sujetos en edades entre 30 y 62 años. En el grupo A se encontró un 41,94% de pacientes normales, 38,71% con sobrepeso, 12,9% con obesidad tipo 1 y 6,45% con déficit. En el grupo B todos los controles eran nutricionalmente sanos. El FCI-1 en el grupo A fue de 47+22ng/ml y en controles 79+33 ng/ml p < 0,05. Conclusión: los niveles sericos de F CI-1 son estadísticamente menores (p < 0,05) en pacientes con enfermedad hepática crónica compensada que en controles sanos, y parecen relacionarse con el grado de malnutrición.

Patients with chronic liver disease have malnutrition in variable degrees. One of the factors implied in malnutrition is the deficiency of insulin growth factor type 1. Objective: to determine the relationship of insulin-like growth factor 1 and malnutrition in patients with compensated chronic liver disease. Materials and methods: group A: 31 patients with chronic liver disease Child Pugh A and group B: 16 healthy controls. The patients were submitted to a clinical history, laboratory, anthropometric evaluation and IGF-1 was determined by enzymatic immunoassay technique. T student was applied with the SPSS online program and a value of p < 0.05 was considered statistically significant. Results: group A: 31 patients with chronic liver disease, alcoholic and non alcoholic, ages between 40 and 66 years, group B: control 16 healthy individuals, with ages between 30 and 62 years. In group A 41.94% of patients were normal, 38.71% with overweight, 12.9% with obesity type 1 and 6.45% with deficit. In group B all the controls were healthy, nutritionally. IGF- 1 in group A was 47 + 22ng/ml and in controls 79 + 33ng/ml p < 0.05. Conclusion: The serum levels of IFG-1 are statistically lower (p< 0.05) in patients with compensated chronic liver disease than in healthy controls and they seem to be related with the malnutrition degree.

Growth in Children with Growth Hormone Deficiency Following Surgery for Craniopharyngioma / 대한소아내분비학회지

PURPOSE: Most children who have been treated for craniopharyngioma eventually develop multiple pituitary hormone deficiencies as well as growth hormone deficiency(GHD). However, some of them may grow normally or even have accelerated growth velocity despite GHD postoperatively. This study was undertaken to evaluate several factors influencing change in growth velocity after surgery for craniopharyngioma in patients with GHD. METHODS: Fifteen patients operated on for craniopharyngioma had a pharmacological assessment of hypothalamic-pituitary function and at least two standard GH provocation tests. All patients had multiple pituitary hormone deficiencies including GHD after surgery. Patients were classified in two groups according to their growth rate during the first postoperative year. Group 1 consisted of 6 children with normal growth velocity or more than 2 standard deviation score(SDS) above the normal mean, and group 2 consisted of 9 children with decreased growth velocity more than 2 SDS below the normal mean. RESULTS: Height velocity was 8.3+/-.2 cm/year in group 1 and 2.8+/-.3 cm/year in group 2 during the first year. During the second year, height velocity was 4.4+/-.3 cm/year and 3.3+/-.4 cm/year, respectively. Body mass index(BMI) change between before and after surgery was 0.83+/-.4 kg/m2 in group 1 and 0.03+/-.3 kg/m2 in group 2 but there was no difference between both groups. However, BMI changes was correlated positively with height SDS change for 1 year following surgery in 15 patients(P<0.05, r=0.601). Prolactin levels before surgery were not significant difference between group 1 and group 2. However, there was a significant positive correlation between prolactin levels before surgery and height SDS change(P<0.01, r=0.671). Postoperative IGF-1 levels were low in all patients except one, who showed decreased growth rate. CONCLUSION: In this study, there were no significant differences in height velocity, BMI, prolactin, and IGF-1 levels between normal growth group and growth failure group after surgery. Further studies are needed to find out any other growth promoting factors related to growth without growth hormone.