OBJECTIVETo identify the changes in serum insulin like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) in children with nephrotic syndrome (NS) and the effect of glucocorticoid on serum IGF-I and IGFBPs.

METHODSWe measured serum IGF-I and IGFBPs levels by radioimmune assay and immune radiomagnetic assay in 36 children with NS, consisting of an active stage group (ANS, n = 12), a remission stage group (RE, n = 12), an active stage group with glucocorticoid treatment (GNS, n = 12), and a normal control group (NC, n = 10).

RESULTS1) Compared to NC, serum levels of IGF-I and IGFBP-3 were decreased (P < 0.01); serum levels of IGFBP-1 and IGFBP-2 were increased (P < 0.01) in the ANS group. 2) Serum levels of IGF-I and IGFBP-3 were higher and IGFBP-1 and IGFBP-2 were lower in the RE Group than in theANS Group (P < 0.01). 3) Compared to the ANS group, serum levels of IGF-I and IGFBP-3 were increased (P < 0.01) and serum levels of IGFBP-1 and IGFBP-2 were decreased (P < 0.01) in the GNS group. 4) A correlation was found between serum levels of IGFBP-3 and albumin in the active stage group (r = 0.76, P < 0.01). There was also a correlation between serum levels of IGF-I and IGFBP-3 and an inverse correlation between the serum level of IGF-I and serum levels of IGFBP-1 and IGFBP-2 in the ANS group. No other correlations were observed.

CONCLUSIONSThe serum levels of IGF-I and IGFBPs are altered in children in the active stage of NS, but return to normal in the remission stage. GC treatment may influence serum IGF-I and IGFBPs in children with NS. Changes in IGF-I and IGFBPs levels may play a role in the growth retardation of NS children.

Child ; Dexamethasone ; pharmacology ; Female ; Glucocorticoids ; pharmacology ; Humans ; Insulin-Like Growth Factor Binding Proteins ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Nephrotic Syndrome ; blood

OBJECTIVETo explore the effects of amino acid solution and recombinant human growth hormone on growth hormone/insulin like growth factor-1 (GH/IGF-1) axis after partial hepatectomy in rats with liver cirrhosis.

METHODSSix normal rats severed as normal group, while 30 rats with liver cirrhosis were randomly divided into preoperation group, 1 day postoperative group, 8.5% Novamin PN for 5 days postoperative group, 10% Hepa PN for 5 days postoperative group and rhGH + 10% Hepa PN for 5 days postoperative group. Liver function, blood glucose and serum GH, IGF-1, IGFBP-3 were determined. ALB mRNA, IGF-1 mRNA and IGFBP-3 mRNA levels in liver tissues were detected by RT-PCR. Liver Ki67 immunohistochemistry staining was studied.

RESULTSCompared with the 8.5% Novamine PN group, serum ALT [(103 +/- 23) IU/L vs (154 +/- 45) IU/L], ALP [(571 +/- 92) IU/L vs (972 +/- 252) IU/L], GH [(1.55 +/- 0.12) ng/ml vs (1.81 +/- 0.11) ng/ml] level were lower (P < 0.05), serum IGF-1 [(966 +/- 55) ng/ml vs (813 +/- 43) ng/ml] and IGFBP-3 [(8.1 +/- 0.3) ng/ml vs (6.9 +/- 0.2) ng/ml] level and the expression of hepatic ALB mRNA (1.24 +/- 0.06 vs 1.02 +/- 0.09), IGF-1 mRNA (0.85 +/- 0.00 vs 0.60 +/- 0.03), IGFBP-3 mRNA (0.69 +/- 0.02 vs 0.58 +/- 0.09) were higher in the 10% Hepa PN group (P < 0.05), but there was no difference in liver Ki67 labeling index [(4.8 +/- 0.3)% vs (4.4 +/- 0.4%)] (P > 0.05). Compared with the 10% Hepa PN group, serum ALP [(434 +/- 41) IU/L vs (571 +/- 92) IU/L] was much lower (P < 0.05), serum ALB [(37.0 +/- 1.8) g/L vs (32.8 +/- 1.2) g/L], blood glucose [(7.6 +/- 1.3) mmol/L vs (4.9 +/- 0.7) mmol/L], GH [(3.00 +/- 0.61) ng/ml vs (1.55 +/- 0.12) ng/ml], IGF-1 [(1100 +/- 32) ng/ml vs (966 +/- 55) ng/ml], IGFBP-3 [(9.3 +/- 0.2) ng/ml vs (8.1 +/- 0.3) ng/ml] level, the expression of hepatic ALB mRNA (1.35 +/- 0.04 vs 1.24 +/- 0.06), IGF-1 mRNA (0.97 +/- 0.00 vs 0.85 +/- 0.00) and liver Ki67 labeling index [(5.4 +/- 0.3)% vs (4.8 +/- 0.3%)] were higher (P < 0.05) in the rhGH + 10% Hepa PN group.

CONCLUSIONSAmino acid solution and recombinant human growth hormone can influence the GH/IGF-1 axis in rats with liver cirrhosis. It may be helpful in selecting and evaluating nutrient by measuring the serum IGF-1 and IGFBP-3 level.

Amino Acids ; pharmacology ; therapeutic use ; Animals ; Human Growth Hormone ; pharmacology ; therapeutic use ; Insulin-Like Growth Factor Binding Protein 1 ; blood ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Liver Cirrhosis, Experimental ; blood ; therapy ; Male ; Parenteral Nutrition, Total ; methods ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; pharmacology ; therapeutic use

To investigate the role of connective tissue growth factor (CTGF) in transdifferentiation of human renal tubular epithelial cell (HKC), in vitro cultured HKC cells were divided into 3 groups: negtive control, low dose CTGF-treated group (rh CTGF, 2.5 ng/ml) and high dose CTGF-treated (rhCTGF, 5.0 ng/ml). Then the expression of alpha-smooth muscle actin (alpha-SMA) were assessed by indirect immuno-fluorescence, and the percentage of alpha-SMA positive cells were assessed by flow cytometry. RT-PCR were also performed to examine the mRNA level of alpha-SMA. Upon the stimulation of different concentrations of rhCTGF, the expression of alpha-SMA were markedly stronger than that in negative controls. The percentages of alpha-SMA positive cells were significantly higher in the stimulated groups than that of negative controls (38.9%, 65.5% vs 2.4%, P<0.01). alpha-SMA mRNA levels were also up-regulated by the stimulation of rhCTGF (P<0.01). These results suggest that CTGF can promote the transdifferentiation of human renal tubular epithelial cells towards myofibroblast (Myo-F).
Actins ; metabolism ; Cell Differentiation ; drug effects ; Cells, Cultured ; Connective Tissue Growth Factor ; Epithelial Cells ; cytology ; Humans ; Immediate-Early Proteins ; pharmacology ; Insulin-Like Growth Factor Binding Proteins ; pharmacology ; Intercellular Signaling Peptides and Proteins ; pharmacology ; Kidney Tubules ; cytology

To investigate the role of connective tissue growth factor (CTGF) in transdifferentiation of human renal tubular epithelial cell (HKC), in vitro cultured HKC cells were divided into 3 groups: negtive control, low dose CTGF-treated group (rh CTGF, 2.5 ng/ml) and high dose CTGF-treated (rhCTGF, 5.0 ng/ml). Then the expression of alpha-smooth muscle actin (alpha-SMA) were assessed by indirect immuno-fluorescence, and the percentage of alpha-SMA positive cells were assessed by flow cytometry. RT-PCR were also performed to examine the mRNA level of alpha-SMA. Upon the stimulation of different concentrations of rhCTGF, the expression of alpha-SMA were markedly stronger than that in negative controls. The percentages of alpha-SMA positive cells were significantly higher in the stimulated groups than that of negative controls (38.9%, 65.5% vs 2.4%, P<0.01). alpha-SMA mRNA levels were also up-regulated by the stimulation of rhCTGF (P<0.01). These results suggest that CTGF can promote the transdifferentiation of human renal tubular epithelial cells towards myofibroblast (Myo-F).
Actins/metabolism ; Cell Differentiation/*drug effects ; Cells, Cultured ; Epithelial Cells/*cytology ; Immediate-Early Proteins/*pharmacology ; Insulin-Like Growth Factor Binding Proteins/pharmacology ; Intercellular Signaling Peptides and Proteins/*pharmacology ; Kidney Tubules/*cytology

cDNA for Insulin-like growth factor binding protein 3 was cloned and constructed a prokaryotic expression vector--pET-DsBA-IGFBP3. The construct was transformed into E. coli BL21 (DE3)plysS. The induced fusion protein (D-IGFBP3) was expressed successfully in soluble form. We obtained D-IGFBP3 the purify of which is over 95% after purification by His affinity chromatography. The product was identified by Western-blot. The cell assay showed that the obtained fusion protein can inhibit the growth of MCF-7 and bind with IGF-I in vitro.
Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chromatography, Affinity ; Dose-Response Relationship, Drug ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Escherichia coli ; genetics ; Gene Expression ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; genetics ; metabolism ; pharmacology ; Insulin-Like Growth Factor I ; metabolism ; Protein Binding ; Recombinant Proteins ; isolation & purification ; metabolism ; pharmacology ; Solubility

Animals ; Chicory ; Fibronectins ; metabolism ; Insulin-Like Growth Factor Binding Proteins ; metabolism ; Liver ; drug effects ; metabolism ; Liver Cirrhosis, Experimental ; metabolism ; Male ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar ; Smad3 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo explore the mechanism of action of tanshinone II A for liver protection in hepatic fibrotic mice by observing its effects on signaling pathway of insulin-like growth factor binding protein 7 (IGFBP7) and TGFbeta1/Smad3.

METHODSHepatic fibrosis model was induced by intraperitoneal injection of thioacetamide (TAA). Thirty-six male Kunming mice were divided into five groups: the normal control group (N), the 4-week model group (A), the 4-week tanshinone II A prevented group (B), the 6-week model group (C) and the 3-week tanshinone II A treated group (D). Changes of serum levels of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH), histopathology of liver (HE staining), area density of collagen in liver (Masson staining), expressions of alpha-smooth muscle actin (alpha-SMA), collagen I , fibronectin (FN), transforming growth factor-beta1 (TGF-beta1), Smad3 and IGFBP7 in liver (by immunohiStochemistry), liver content of FN, Smad3 and IGFBP7 (by Western blot), and the hepatocyte apoptosis (by TUNEL) were observed.

RESULTSThe serum levels of ALT and LDH, the expressions of alpha-SMA, collagen I , TGF-beta1 in liver, expressions and contents of FN, Smad3 and IGFBP7 in liver were significantly lower; the liver damage and the hepatic apoptosis index were lesser in Group B than in Group A, also in Group D than in Group C, respectively, all showing statistical significance (P < 0.05).

CONCLUSIONTanshinone II A could improve liver function, inhibit the activation of hepatic stellate cells, reduce the production of extracellular matrix, and protect the hepatocytes, and its of mechanisms of actions might be related with blocking TGF-beta1/Smad3 signaling pathway and down-regulating the expression of IGFBP7 in liver.

Animals ; Diterpenes, Abietane ; pharmacology ; Hepatic Stellate Cells ; drug effects ; metabolism ; Hepatocytes ; drug effects ; metabolism ; Insulin-Like Growth Factor Binding Proteins ; metabolism ; Liver Cirrhosis, Experimental ; metabolism ; Male ; Mice ; Mice, Inbred Strains ; Signal Transduction ; Smad3 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo investigate the effects of early nutritional intervention on the serum insulin-like growth factor-1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), intestinal development, and catch-up growth of intrauterine growth retardation (IUGR) rats by giving the IUGR new born rats different protein level diet.

METHODSIUGR rat model was built by starvation of pregnant female rats. Twenty-four IUGR pups and 8 normal pups were divided randomly into 4 groups: normal control group (C group); IUGR control group (S group), IUGR low-protein diet group (SL group), and IUGR high-protein diet group (SH group). Detected the serum IGF1, IGFBP3, body weight, body length, intestinal weight length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT), and disaccharidase at the 4th week.

RESULTS(1) The SH group showed the fastest catch-up growth, serum IGF1, IGFBP3, VH, and VSA were significantly higher than those of normal control group and IUGR control group. The intestinal weight and length, and the activities of lactase and saccharase of the SH group also reached the normal control group level. (2) The SL group kept on small size, the serum IGF1, IGFBP3, and most of intestinal histological indexes were all significantly lower than other groups. (3) IGF1, IGFBP3 were positively correlated to intestinal VH, VSA, saccharase, body weight and length.

CONCLUSIONSThe serum IGF1 was a sensitive index to the catch-up growth. The early nutritional intervention of high-protein diet after birth is helpful for the catch-up growth of IUGR through promoting the intestinal development and the absorption of nutrition.

Animals ; Animals, Newborn ; growth & development ; Body Weight ; drug effects ; Dietary Proteins ; pharmacology ; Female ; Fetal Growth Retardation ; blood ; etiology ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Intestines ; growth & development ; pathology ; Nutritional Physiological Phenomena ; Pregnancy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of inositol hexaphosphate (IP6) on proliferation of human prostate carcinoma LNCaP cells and its relation to insulin-like growth factors binding protein-3 (IGFBP-3) expression.

METHODSThe siRNA technology was used to silence the IGFBP-3 gene in LNCaP cells. LNCaP cells and IGFBP-3 gene silenced LNCaP cells were exposed to IP6 for 24 h. Cell viability was measured by MTT assay; cell cycle arrest and cell apoptosis were detected by flow cytometry. The expression levels of IGFBP-3 and Bcl-2 mRNA and protein were analyzed by real-time quantitative RT-PCR and Western blotting, respectively.

RESULTSThe proliferation of LNCaP cells was be inhibited by IP6 in a dose dependent manner. After exposure to IP6 for 24 h, the cell viability in LNCaP cells and siRNA-treated LNCaP cells was 53.2%±11.6% and 82.3%±10.9%, respectively (P<0.05). After treatment of 1.5 mmol IP6，the apoptosis rate of LNCAP cells and siRNA-treated LNCAP cells was 40.48%±13.21% and 30.43%±10.65%, respectively (P<0.05). The proportion of G1 and G2 phase in LNCAP cells was 70.58%±8.25% and 5.64%±1.23%，after IP6 treatment the percentage of G1 phase cells decreased to 48.66%±11.23% and G2 phase cells increased to 31.11%±9.68%. However, for siRNA treated LNCAP cells, the proportion of G1 phase cells was 58.25%±12.36% and G2 phase cells was 23.85%±12.45%. Higher expression of IGFBP-3 and lower expression of Bcl-2 in LNCaP cells treated with IP6 were found at both mRNA and protein levels. IP6 treatment enhanced IGFBP-3 mRNA expression by 2.21±0.15 folds. In the contrast, expression of Bcl-2 mRNA decreased by 0.69±0.03 folds. Meanwhile, after IGFBP- gene silence Bcl-2 expression was not decreased.

CONCLUSIONIP6 can inhibit the proliferation of LNCaP cells, which may be associated with the changes of IGFBP-3 level through Bcl-2 expression.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Gene Silencing ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; metabolism ; Male ; Phytic Acid ; pharmacology ; Prostatic Neoplasms ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Small Interfering

Alanine Transaminase ; blood ; Animals ; Antibodies ; pharmacology ; Apoptosis ; Collagen Type I ; biosynthesis ; DNA-Binding Proteins ; metabolism ; Disease Models, Animal ; Insulin-Like Growth Factor Binding Protein 1 ; immunology ; L-Lactate Dehydrogenase ; blood ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; drug therapy ; immunology ; metabolism ; Male ; Mice ; Protective Agents ; pharmacology ; Thioacetamide ; Transforming Growth Factor beta ; metabolism