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

Insulin-like growth factor I (IGF I), a potent growth factor in vitro, is present in blood and in multiple tissues and is a major mediator of the effects of growth hormone on postnatal growth. IGF I is internalized and retained largely intact in cultured vascular endothelial cells. Neovasculature transiently expresses IGF I immunoreactivity, but it is not known whether this represents internalization of the circulating growth factor or vascular cell synthesis of IGF I. As an initial approach to defining the role of endogenous production of IGF I in the growth program of the vessel wall, Northern hybridizations were performed with RNA from cultured rat aortic smooth muscle cells and bovine aortic endothelial cells. Rat aortic smooth muscle cells expressed three primary IGF I messenger RNA transcripts sized 8.2, 1.7, and 0.9-1.2 kb. Bovine aortic endothelial cells expressed one major and one minor IGF I transcript of 2.1 and 1.6 kb, respectively. IGF I gene expression in smooth muscle cells was also demonstrated by ribonuclease protection assays using a rat exon 3 riboprobe. Both endothelial and vascular smooth muscle cells secreted IGF I, as detected by radioimmunoassay of conditioned medium after separation of IGF I from its binding proteins by gel filtration chromatography. Because IGF I stimulates growth of vascular cells, characterization of IGF I gene expression in blood vessels may be key to understanding developmental as well as abnormal growth in the cardiovascular system.
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PMID:Insulin-like growth factor I gene expression in vascular cells. 170 44

Insulin-like growth factor I (IGF-I) stimulates hematopoiesis. We examined whether bone marrow stromal cells synthesize IGF-I. Secretion of IGF-I immunoreactivity by cells from TC-1 murine bone marrow stromal cells was time-dependent and inhibited by cycloheximide. Gel filtration chromatography under denaturing conditions of TC-1 conditioned medium demonstrated two major peaks of apparent IGF-I immunoreactivity with molecular weights of approximately 7.5-8.0 kD, the size of native IGF-I, and greater than 25 kD. Expression of IGF-I mRNA was identified by both RNase protection assay and reverse transcription/polymerase chain reaction. To determine whether the greater than 25-kD species identified by RIA possessed IGF-binding activity, a potential cause of artifactual IGF-I immunoreactivity, charcoal adsorption assay of these gel filtration fractions was performed. The peak of IGF-binding activity coeluted with apparent IGF-I immunoreactivity suggesting that TC-1 cells secrete IGF-binding protein(s). Unfractionated conditioned medium exhibited linear dose-dependent increase in specific binding of [125I]-IGF-I with a pattern of displacement (IGF-I and IGF-II much greater than insulin) characteristic of IGF-binding proteins. Western ligand analysis of conditioned medium showed three IGF-I binding species of approximately 31, 38, and 40 kD. These data indicate that TC-1 bone marrow stromal cells synthesize and secrete IGF-I and IGF-binding proteins and constitute a useful model system to study their regulation and role in hematopoiesis.
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PMID:Secretion of insulinlike growth factor I and insulinlike growth factor-binding proteins by murine bone marrow stromal cells. 171 20

Insulin-like growth factor I (IGF-I) mRNA was demonstrated in primary cultures of neuronal and glial cells from rat brain. On Northern blots, a rat IGF-I cDNA probe hybridized to RNA species of 7.5, 1.7, and 0.8-1.2 kilobases in total and poly(A)+ RNA from both cell types. Solution hybridization/RNase protection assays were performed using an antisense riboprobe complementary to the 5'-untranslated region as well as part of the coding region of rat IGF-I mRNA. These studies indicated that two of the previously described three possible alternative 5'-untranslated splicing variants (classes A and C) were expressed in neuronal and glial cells, with class C transcripts predominating. Neuronal cells also possessed extremely low levels of class B transcripts. Treatment of neuronal cell cultures with the synthetic glucocorticoid dexamethasone reduced IGF-I mRNA levels by 60%. Glial cell IGF-I mRNA levels were reduced by dexamethasone by up to 40%. These results suggest that glucocorticoid-induced reductions in IGF-I production could occur at the level of transcription and may underlie some of the actions of glucocorticoids in causing growth retardation and inhibition of cell proliferation.
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PMID:Dexamethasone reduces steady state insulin-like growth factor I messenger ribonucleic acid levels in rat neuronal and glial cells in primary culture. 245 16

Insulin-like growth factor I (IGF-I) activity has been reported to be produced by several human cancers. Identification of RNAs transcribed from the IGF-I gene has been complicated by the detection of multiple hybridizing bands on Northern analysis. To determine if any of these RNAs are transcribed from the IGF-I gene, we have used a sensitive and specific ribonuclease (RNAse) protection assay for IGF-I. We have also studied the breast cancer tissue expression of IGF-I using in situ hybridization histochemistry. We have found no IGF-I mRNA in breast (zero of 11) or colon cancer (zero of 9) cell lines; both of these tumors have been previously reported to express IGF-I mRNA. However, three of three neuroepithelioma and one of two Ewing's sarcoma cell lines express IGF-I mRNA; therefore, in these tumors IGF-I may be an autocrine growth factor. In contrast to breast cancer cell lines, RNA extracted from breast tissues has easily detectable IGF-I mRNA. In situ hybridizations show that IGF-I mRNA is expressed in the stromal cells, and not by normal or malignant epithelial cells. These findings suggest that although IGF-I is not produced by breast epithelial cells it may function as either a paracrine stimulator of epithelial cells or an autocrine stimulator of stromal cells.
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PMID:Analysis of insulin-like growth factor I gene expression in malignancy: evidence for a paracrine role in human breast cancer. 274 57

Insulin-like growth factor I (IGF-I) is a widely expressed abundant autocrine and paracrine factor that regulates the proliferation and differentiation of a variety of cell types. Prostaglandin E2 (PGE2) is a potent stimulator of IGF-I synthesis in bone. We examined the regulation of IGF-I synthesis by PGE2 in osteoblast-enriched (Ob) cells from fetal rat calvaria. PGE2 treatment of Ob cells at 1 microM for 2 h resulted in a 5-fold increase in heterogeneous nuclear RNA levels, as measured by a reverse transcriptase-polymerase chain reaction assay, suggesting an increase in IGF-I gene transcription. RNase protection analysis was used to map the transcriptional start sites in the IGF-I gene that are used in Ob cells. Consistent with other extrahepatic tissues, initiation of transcription occurs primarily at three sites within the 5'-regions of exon 1 of the IGF-I gene. PGE2 treatment did not alter start site usage. The regions upstream of these transcriptional start sites were analyzed by transiently transfecting Ob cells with putative rat IGF-I promoter sequences ligated to a luciferase reporter gene. Constructs containing 1.4 kilobases of the 5'-regions regions of exons 1 and 2 had significant promoter activity. PGE2 treatment of transfected Ob cells increased luciferase activity 5-fold when a 1.4-kilobase exon 1 promoter fragment was tested. This increase in luciferase activity was time and dose dependent. Smaller regions of the exon 1 promoter sequence gave higher basal activity and were less responsive to PGE2. We conclude that regions involved in IGF-I regulation by PGE2 are contained within the IGF-I promoter.
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PMID:Regulation of insulin-like growth factor I transcription by prostaglandin E2 in osteoblast cells. 782 49

Molecular mechanisms regulating the cardiac hypertrophic response to increased hemodynamic load are understood poorly. Insulin-like growth factor I (IGF I) is a mitogen that is thought to play a key role in pre- and postnatal growth. To investigate a possible role of IGF I in the cardiac response to pressure overload, rats underwent banding of the ascending aorta immediately above the aortic valve using a hemoclip, or a sham procedure. An analysis of left-ventricular RNA by Northern hybridization using a 32P-labeled IGF I cDNA revealed four messenger ribonucleic acid transcripts of 7.6, 4.6, 1.7, and 0.9 to 1.2 Kb. Insulin-like growth factor I messenger ribonucleic acid was quantitated by ribonuclease protection assays using a rat exon 3 riboprobe. There was a sustained increase in IGF I mRNA levels that correlated temporally with the development of left ventricular hypertrophy. These results indicate that left ventricular pressure overload is associated with an induction of cardiac IGF I gene expression. Insulin-like growth factor I may play a role in the response to increases in wall stress and likely contribute to cardiac hypertrophy.
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PMID:Induction of cardiac insulin-like growth factor I gene expression in pressure overload hypertrophy. 836 94

Growth and differentiation of the mammary gland during development and lactation are controlled by complex hormonal mechanisms. Additionally growth factors are supposed to act as local mediators of the hormonally controlled developmental processes. Mammary tissue for this study was obtained from non pregnant control heifers, primigravid heifers (second part of pregnancy), around parturition, during lactation (early and late) and from dry cows. Using RT-PCR and ribonuclease protections assay (RPA) the expression of the following growth factors was studied in the different phases bovine mammary gland development: Insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), fibroblast growth factor 1 (FGF-I), fibroblast growth factor 2 (FGF-2), transforming growth factor alpha (TGF-alpha). Additionally the expression of fibroblast growth factor receptor (FGFR) and growth hormone receptor (GHR) was investigated. The cellular distribution pattern of several of these growth factors and GHR was obtained using Immunocytochemical techniques. The detailed expression and localization pattern of these growth factors are presented and their role in the local regulation of the bovine mammary gland is briefly discussed.
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PMID:Expression and localization of growth factors during mammary gland development. 1095 6

Testosterone is known to act differentially on skeletal muscle from different regions of the body. Two genes likely to mediate the testosterone effect are insulin-like growth factor I (IGF-I), an important growth regulator acting in an autocrine and paracrine way, and androgen receptor (AR), because receptor density could account for differential muscle growth. Another muscle-specific gene that may play a role in differential muscle growth is myostatin, a member of the transforming growth factor-beta superfamily, shown to be a negative regulator of skeletal muscle mass. The objective of this study was to quantify and compare the steady state expression of these three genes in two different skeletal muscles in sheep. Eleven Dorset rams were slaughtered after reaching puberty and total RNA was extracted from samples of semitendinosus and splenius muscles. Insulin-like growth factor I mRNA was measured using a competitive reverse-transcription-polymerase chain reaction. Androgen receptor and myostatin mRNA were measured by a ribonuclease protection assay (RPA) with standard curves. The means (attomoles/microg RNA) for splenius and semitendinosus muscles were 1.39 and 1.02 (SE = 0.14), 4.05 and 2.96 (SE = 0.24), and 4.30 and 3.85 (SE = 0.37) for IGF-I, AR, and myostatin, respectively. The difference between the two muscles was significant for IGF-I and AR mRNA levels with higher levels in the splenius but not significant for myostatin. Our results show that locally produced IGF-I and the regulation of AR expression may be important for sexually dimorphic muscle growth patterns.
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PMID:Gene expression in sexually dimorphic muscles in sheep. 1216 55