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)

Ovarian follicular growth and steroidogenesis are controlled by the interaction of insulin-like growth factors (IGFs) and gonadotropins. The objective was to determine the temporal and spatial relationships for gonadotropin receptor, steroidogenic enzyme, and IGF system gene expression during the development of preovulatory porcine follicles. Sows (n = 18) were weaned and follicles were monitored by transrectal ultrasonography. Ovaries were collected from sows when the mean diameter of the preovulatory follicular cohort was approximately 2, 4, 6, or 8 mm. mRNA were measured by in situ hybridization for individual follicles within the preovulatory cohort (3 to 5 follicles per sow). Patterns of gene expression detected by in situ hybridization were confirmed by RNase protection analyses of pooled RNA samples. The amount of LH receptor mRNA and steroidogenic enzyme mRNA (17alpha-hydroxylase and aromatase) increased as the mean diameter of the follicular cohort increased from 2 to 6 mm, but then decreased abruptly for 8-mm follicles. Estradiol concentrations in follicular fluid closely followed the expression patterns of steroidogenic enzymes and LH receptor mRNA. FSH receptor mRNA was present in cohorts of 2-mm follicles but declined in 4-mm follicles and was undetectable in 6- and 8-mm follicles. The expression of IGF-I and type I IGF receptor mRNA were similar for follicles of 2, 4, 6, and 8 mm. In contrast, IGF-II mRNA progressively increased in follicles collected from 2-, 4-, and 6-mm cohorts, and then decreased slightly at 8 mm. Type II IGF receptor mRNA was greatest in 8-mm follicles. IGF binding protein-2 (BP-2) mRNA decreased as follicles achieved progressively larger sizes during the preovulatory period (2 to 8 mm), whereas the IGFBP-4 mRNA remained relatively low for follicles in 2- to 6-mm cohorts but then increased markedly in 8-mm follicles. In summary, temporal and spatial patterns of gene expression for gonadotropin receptor, steroidogenic enzyme, and IGF system genes were characterized in preovulatory porcine follicles by using in situ hybridization and RNase protection analyses. The unique patterns of gene expression suggest interdependence among specific genes that may be essential for preovulatory follicular development.
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PMID:Growth and the initiation of steroidogenesis in porcine follicles are associated with unique patterns of gene expression for individual componentsof the ovarian insulin-like growth factor system. 1095 42

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

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 inflammatory response of the lung to noxious factors contributes to the pathogenesis of chronic lung injury. Inflammatory mediators regulate the insulin-like growth factor (IGF) system, a key modulator of lung fibroblast proliferation. The activity of IGFs is regulated by IGF-binding proteins (IGFBPs) secreted by lung cells. To investigate the regulation of lung fibroblast IGFBPs by cytokines, we exposed 19-d fetal rat lung fibroblasts to various pro- and anti-inflammatory mediators. IGFBP abundance in conditioned medium (CM) was measured by ligand blot and RNA transcript abundance by RNase protection assays. Fetal rat lung fibroblasts exposed to interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha for 48 h demonstrated increased abundance of CM IGFBP-3 (5.9- and 4.7-fold increases for IL-1beta and TNF-alpha, respectively) and IGFBP-4 (5.7- and 7.4-fold increases for IL-1beta and TNF-alpha, respectively) that was accompanied by a small increase in IGFBP-4 mRNA and a larger increase in IGFBP-3 mRNA abundance. IGFBP-4 specific proteolysis was examined in CM collected from fetal rat lung fibroblasts after incubation with serum-free medium (SFM), IL-1beta, or TNF-alpha for 48 h. Cell-free aliquots of SFM-CM incubated at 37C for 24 h showed a 65% decrease in IGFBP-4 abundance that was inhibited by 1,10-phenanthroline. In contrast, CM from cells exposed to IL-1beta or TNF-alpha incubated at 37 degrees C for 24 h did not show a significant decrease in IGFBP-4 abundance unless IGF-I was present during the cell-free incubation. Addition of IGFBP-3 to aliquots of SFM-CM reversed the IGF-I-mediated acceleration of IGFBP-4 proteolysis. Similarly, addition of IGFBP-3 to cells in culture increased the accumulation of CM IGFBP-4. These results demonstrate that cytokines regulate IGFBP production and clearance by fetal lung cells and suggest a mechanism by which cytokines regulate cell proliferation following lung injury.
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PMID:Pro- and anti-inflammatory cytokines regulate insulin-like growth factor binding protein production by fetal rat lung fibroblasts. 1186 36


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