Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The components of the insulin-like growth factor (IGF) axis have been investigated in the normal human thymus. Using ribonuclease protection assays (RPA), IGF-II transcripts were detected in the normal human thymus. By reverse transcriptase polymerase chain reaction (RT-PCR) analyses, promoters P3 and P4 were found to be active in the transcription of IGF2 gene within human thymic epithelial cells (TEC). No IGF-II mRNA could be detected in human lymphoid Jurkat T cells with 30 cycles of RT-PCR. By Northern blot analyses, IGFBP-2 to -6 (but not IGFBP-1) were found to be expressed in TEC with a predominance of IGFBP-4. Interestingly, Jurkat T cells only express IGFBP-2 but at high levels. The type 1 IGF receptor was detected in Jurkat T cells but not in human TEC. The identification of the components of the IGF axis within separate compartments of the human thymus adds further evidence for a role of this axis in the control of T-cell development. The precise influence of thymic IGF axis upon T-cell differentiation and immunological self-tolerance however needs to be further investigated.
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PMID:Characterization of the insulin-like growth factor axis in the human thymus. 1033 24

Insulin-like growth factor-binding proteins (IGFBPs) both stimulate and inhibit IGF activity, and in the M12 prostate cancer cell line, overexpression of IGFBP-4 was shown to delay tumorigenesis while decreasing the production of IGFBP-2. We have performed the reverse experiment, inhibition of IGFBP-4 expression with antisense complementary DNA, in two prostate tumor cell lines, ALVA-31 and M12. Expression of antisense messenger RNA transcripts was verified by RNase protection assays, and inhibition of mature IGFBP-4 in cell medium was demonstrated by Western blotting. Both transfected lines (ALVA-31asBP4 and M12asBP4) proliferated more slowly in monolayer culture than parental controls. Colony formation in soft agar was strongly inhibited in both cases, and the rate of tumor formation and growth in male athymic nude mice injected with M12asBP4 was markedly reduced relative to that in mice receiving M12 control cells. Apoptosis induced by the topoisomerase inhibitor etoposide was also enhanced in transfected cells. The effects on colony formation in soft agar and tumor formation in mice were maintained for the duration of the experiments, in contrast to the delayed growth observed in the previous study of IGFBP-4 overexpression. A significant difference was found in the patterns of IGFBP expression; production of both messenger RNA and protein for IGFBP-3 and IGFBP-6 was greatly increased in the M12asBP4 and ALVA31asBP4 cell lines. Up-regulation of these binding proteins has been observed in association with actions of 1,25-dihydroxyvitamin D(3) in prostate cancer cells, and the data suggest a role for IGFBP-3 and IGFBP-6 in the suppression of prostate tumor cell growth.
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PMID:Inhibition of growth and increased expression of insulin-like growth factor-binding protein-3 (IGFBP-3) and -6 in prostate cancer cells stably transfected with antisense IGFBP-4 complementary deoxyribonucleic acid. 1131 65

While transforming growth factor-beta1 (TGF-beta1) regulates proliferation and differentiation of human osteoblast precursor cells, the mechanisms underlying these effects are not known. Several hormones and locally acting growth factors regulate osteoblast functions through changes in the insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs). Thus, we studied the effects of TGF-beta1 on IGFs and IGFBPs in human marrow stromal (hMS) osteoblast precursor cells. TGF-beta1 increased the steady-state mRNA level of IGF-I up to 8.5+/-0.6-fold (P<0.001) in a dose- (0.1-10 ng/ml), and time-dependent (12-72 h) manner. No significant effects on IGF-II gene expression were detectable. Employing RNase protection and nuclear run-on assays, these effects on IGF-I were found to take place at the transcriptional level and were not dependent on de novo protein synthesis. Using the transient transfection of various fragments of the IGF-I promoter 1, we found that TGF-beta responsive elements were present in a promoter fragment ranging from-65 bp to+55 bp relative to the major transcription start site in exon 1. In addition, TGF-beta1 treatment resulted in a dose- and time-dependent increase (2-fold) in the IGFBP-3 steady-state mRNA level as well as in protein production but did not affect IGFBP-2 or IGFBP-4 at mRNA or protein levels. Our results indicate that TGF-beta1 exerts significant effects on stimulatory components of the IGF-system and that may represent a mechanism mediating TGF-beta effects on the biological functions of osteoblasts.
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PMID:Transforming growth factor-beta1 stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors. 1137 25

Summary Insulin-like growth factor-I (IGF-I) is involved in the regulation of growth and differentiation of a variety of vertebrate tissues. The biological actions of IGF-I are mediated mainly by the IGF-I receptor (IGF-IR) and partly by the insulin receptor (IR) and modulated by IGF binding proteins (IGFBP). We conducted studies designed to clarify the possible roles of IGF system in the development of the avian reproductive organs. We cloned cDNAs of IGF-I, IGF-IR, IR and IGFBP-2 of Japanese quail and simultaneously measured the expression of these genes in the quail liver, testis and oviduct at different ages using a lysate RNase protection assay. Hepatic IGF-I mRNA levels increased rapidly and remained elevated during the rapid-growing period, which coincided with the period of rapid increase in testicular weight. IGF-I mRNA was detected at each stage of developing testis examined. Its level was high at the early stage and decreased with age. IGFBP-2 mRNA in testis exhibited a similar expression pattern to that of IGF-I, whereas a divergence in IGF-I and IGF-IR gene expression was observed. Both IGF-IR and IR mRNAs increased when the testis grew rapidly and decreased when sexual maturation was almost completed. These results suggest that IGF-I may serve as an autocrine/paracrine regulator as well as an endocrine regulator in the testicular development and function of Japanese quail. In the oviduct, IGF-I, IGF-IR, IR and IGFBP-2 mRNAs were also developmentally regulated. A rapid growth of the oviduct was accompanied by a significant increase in the level of IGF-I mRNA. The expression of genes encoding IGF-IR, IR and IGFBP-2 in the oviduct exhibited a similar developmental change to that of IGF-I. These results suggest that IGF-I mainly works in an autocrine and/or paracrine manner in the oviduct during the development of this organ. The findings of the present study provide further evidence of an important role for IGF system in the development and function of the avian reproductive system.
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PMID:Developmental changes in the mRNA levels of IGF-I and its related genes in the reproductive organs of Japanese quail (Coturnix coturnix japonica). 1143 71

Mechanical forces are well known to modulate smooth muscle cell growth and synthetic phenotype. The signals controlling this process are complex and potentially involve changes in the expression of peptide growth factor genes such as those of the insulin-like growth factor (IGF) system. This study was designed to investigate the mechanical regulation of IGF-I and the binding proteins for IGF (IGFBPs) in smooth muscle cells cultured on a deformable surface and subjected to cyclic stretch. Using the RNase protection assay, we found that the application of a cyclic biaxial strain to cells induced a 2.5- to 4-fold increase in IGF-I mRNA levels after 8 h and an even greater increase after 16-24 h of stretch. This change was not affected by variations in the magnitude of the applied strain but was attenuated ( approximately 40%) when cells were treated with antagonists for angiotensin II receptors. Furthermore, the transcript levels of the three major IGF binding proteins produced in smooth muscle cells, e.g., IGFBP-2, IGFBP-4, and IGFBP-5, varied between stretched and control cells. Both IGFBP-2 and IGFBP-4 mRNA levels were consistently reduced in stretched cells but remained comparable to those of the control cells when the angiotensin II transducing pathway was blocked by inhibitors prior to the application of mechanical strain. Conversely, the gene expression of IGFBP-5 was upregulated in stretched cells, and neutralizing antibodies to IGF-I blocked this activation. Similarly, pharmacologic inhibition of the phosphatidylinositol 3-kinase, an important component of the IGF receptor transduction pathway, inhibited IGFBP-5 gene expression in stretched cells. These results suggest that the downstream effects of mechanical strain on IGF-I and IGFBP transcript levels are mediated, to greater or lesser extent, either through an angiotensin II tranducing pathway or via a feedback loop involving the autocrine secretion of IGF-I itself.
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PMID:Mechanical regulation of IGF-I and IGF-binding protein gene transcription in bladder smooth muscle cells. 1178 55

The aim of this work was to study the influence of the endocrine balance between thyroid hormones, insulin and growth hormone (GH) on the regulation of insulin-like growth factor binding proteins (IGFBPs), complementing a study previously reported for insulin-like growth factors (IGFs) in similar populations. Serum concentrations of IGFBPs-1 to -3 were assayed by Western ligand blot and their mRNA expression in the liver assayed by RNase protection assay in the hypothyroid populations: thyroidectomized and mercapto-1-methylimidazole (MMI)-treated neonates, and thyroidectomized adult rats at different periods after thyroidectomy. Serum concentrations of insulin, GH and IGF-I were increased in thyroidectomized neonates and decreased in the other populations. IGFBPs-1 and -2 increased 79% and 50% respectively in thyroidectomized neonatal rats compared with control at 15 days after thyroidectomy, whereas only IGFBP-2 increased (87%) in MMI-treated neonates, which had low serum insulin and GH compared with control on the same days. In thyroidectomized adult rats, IGFBPs-1 and -2 decreased 60% compared with controls on all days studied. Furthermore, when streptozotocin was administered to thyroidectomized neonates and insulin was given to thyroidectomized adult rats to restore insulin to control values in both groups, a differential regulation was found for IGFBPs-1 and -2. The transcriptionally induced decrease in IGFBP-3 (20-25% compared with control in neonates and 50% in adult rats), however, seemed to be regulated by GH and IGF-I. The similarity of changes in IGFBPs found in hypothyroid, undernourished and streptozotocin-induced diabetic neonatal rats suggests that the regulatory effect of insulin or GH on the IGFBPs requires the reduced biologically active thyroid hormone that is found in these three populations.
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PMID:Influence of hypothyroidism on circulating concentrations and liver expression of IGF-binding proteins mRNA from neonatal and adult rats. 1183 54

Infusion of pigs with an insulin-like growth factor-I (IGF-I) analogue (LongR(3)IGF-I) that does not bind to IGF-binding proteins decreases growth rate and the plasma concentration of growth hormone (GH), IGF-I, IGFBP-3, and insulin. This study was designed to determine whether the decrease is due to changes in IGF-I and IGFBP-3 gene expression. IGF-I or LongR(3)IGF-I (180 microg/kg/day) was infused into 55-kg finisher pigs for 4 days using Travenol infuser pumps. Plasma IGF-I concentration was measured by radioimmunoassay and plasma IGFBP-3 and IGFBP-2 were estimated by Western ligand blotting. Steady-state levels of IGF-I and IGFBP-3 mRNA were measured by RNase protection assay. Neither IGF-I nor LongR(3)IGF-I had a significant effect on hepatic IGF-I class 1 mRNA expression, whereas hepatic IGF-I class 2 mRNA expression was significantly reduced by both peptides. Plasma IGFBP-3 levels were unaffected by IGF-I treatment but were reduced by LongR(3)IGF-I treatment. The decrease in IGFBP-3 was not due to decreased gene expression in porcine liver or kidney, since neither IGF-I nor LongR(3)IGF-I treatment altered IGFBP-3 mRNA. This study infers a direct effect of the IGF analogue LongR(3)IGF-I on GH through its inhibition of plasma IGF-I concentration and class 2 IGF-I mRNA. The decrease in plasma IGFBP-3 was not accompanied by a decrease in hepatic or renal IGFBP-3 mRNA, suggesting that in this case, plasma IGFBP-3 protein levels are posttranslationally regulated or are derived from tissues other than liver or kidney.
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PMID:Short-term infusion of LongR(3) insulin-like growth factor (IGF)-I decreases hepatic IGF-I mRNA but not IGF binding protein-3 mRNA expression in pigs. 1203 Jul 78


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