Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conventional hormone replacement therapy acts primarily by preserving bone, but cannot restore lost bone in women with established osteoporosis. Studies in rodents have shown that high doses of estrogens have anabolic skeletal effects, and recent observations in a group of women treated long term with high doses of estrogen indicated that similar effects occur in humans. This study examines the hypothesis that locally produced growth factors, including transforming growth factor-beta (TGF-beta) and platelet-derived growth factors (PDGFs), are involved in mediating the anabolic effects of high-dose estrogen. Transiliac-crest bone biopsies were taken from ten women, aged 52-67 years (mean 58 years), who had been treated with high-dose estrogen for 15 years. Control samples were obtained from four age-matched postmenopausal women not receiving estrogen therapy. TGF-betas and PDGFs were analyzed for mRNA and protein expression by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Results showed both TGF-beta1 and -beta2 mRNA, expressed as a ratio to GAPDH, were increased in the estrogen-treated group with an eightfold increase for TGF-beta1 (0.258 +/- 0.246 [mean +/- SD] vs. 0.032 +/- 0.053 in the control group, p = 0.02) and a twofold increase for TGF-beta2 (p = n.s.). TGF-beta3 analysis showed only negligible amounts in both groups. Protein expression levels for TGF-beta1, -beta2, -betaRI and -RII were higher in the estrogen-treated group than in controls, the most marked effects being seen for TGF-beta1. PDGF-A protein expression was also significantly higher in osteoblasts and osteocytes in women treated with estrogen, whereas PDGF-B showed only modest differences. The percentage of bone surface occupied by osteoclasts, as determined by tartrate-resistant acid phosphatase (TRAP) staining, was significantly reduced in the estrogen-treated group (p = 0.001). These results demonstrate that high-dose estrogen therapy is associated with increased TGF-beta, TGF-betaR, and PDGF synthesis and decreased osteoclast activity, consistent with the hypothesis that these growth factors may mediate the actions of estrogen in bone.
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PMID:Mechanisms by which high-dose estrogen therapy produces anabolic skeletal effects in postmenopausal women: role of locally produced growth factors. 1155 64

Cytokines derived from lymphocytes are believed to play key roles in a variety of diseases, including airway diseases such as asthma. The current study was designed to evaluate the hypothesis that cytokines derived from Th2 cells, interleukin (IL)-4 and IL-13, might contribute to tissue remodeling by modulating the production of transforming growth factor (TGF)-beta. In addition, the ability of interferon (IFN)-gamma, a cytokine derived from Th1 cells that can antagonize many effects of IL-4 and IL-13, was also assessed for its effects on TGF-beta production. IL-4 and IL-13 both stimulated production of TGF-beta2 release from human bronchial epithelial cells in a time- and concentration-dependent manner. Both with and without acidification, TGF-beta2 were detected. Neither TGF-beta1 nor TGF-beta3 was released. In contrast to the stimulatory effect on human bronchial epithelial cells, neither IL-4 nor IL-13 stimulated release of any TGF-beta isoform from human lung fibroblasts. IFN-gamma reduced both basal, IL-4-, and IL-13-stimulated release of TGF-beta2 in human bronchial epithelial cells. The stimulatory effects of IL-4 and IL-13 and the inhibitory effect of IFN-gamma on TGF-beta2 release were paralleled by mRNA levels, as assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). In summary, the Th2-derived cytokines, IL-4 and IL-13, can stimulate production of TGF-beta from airway epithelial cells but not from lung fibroblasts. IFN-gamma, in contrast, can inhibit TGF-beta2 release both under basal conditions and following IL-4 or IL-13 stimulation. The ability of these cytokines to modulate TGF-beta release may contribute to both normal airway repair and to the development of subepithelial fibrosis in asthma.
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PMID:Interleukin-4- and interleukin-13-enhanced transforming growth factor-beta2 production in cultured human bronchial epithelial cells is attenuated by interferon-gamma. 1191 85

Adult roe deer males show hormonally controlled seasonal cycles of testicular growth and involution. Mediation of endocrine signals likely requires variable production of testicular growth factors for regulation of testis function. Here we studied the expression pattern of transforming growth factors (TGFs) beta1 and beta3. Total RNA from testis parenchyma was extracted monthly and analysed using quantitative reverse transcriptase PCR. The localization of mRNAs was determined by in situ hybridization, and corresponding proteins were visualized immunohistochemically. Both factors showed different expression levels and different seasonal expression patterns. The TGF-beta1 mRNA content was up to 45 times higher than that of TGF-beta3. Compared with its lowest level in May, TGF-beta1 expression was slightly enhanced during pre-rut (June/July). TGF-beta3 expression increased 5-fold from April to June/July and decreased thereafter to its low in December. This corresponded with changing numbers of spermatocytes and round spermatids, in which both TGF-beta3 mRNA and the protein were mainly localized. The TGF-beta1 mRNA was found in interstitial cells, mainly during the non-breeding season, but also in spermatocytes and spermatids during activated spermatogenesis. The translation product was localized in few spermatogenic cells only. The results suggest that TGF-beta1 and -beta3 are important in regulating seasonal spermatogenesis of roe deer with diverse functions affecting interstitial and spermatogenic cells.
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PMID:Seasonal variation in expression and localization of testicular transforming growth factors TGF-{beta}1 and TGF-{beta}3 corresponds with spermatogenic activity in roe deer. 1629 68

We previously reported evidence that patients with periodontitis have serum antibodies to oral Gram positive bacteria that are cross-reactive with epithelial antigens, including CD24. High level expression of CD24 was confined to the reactive periodontal epithelium and inflamed gingival attachment. As a model for the reactive epithelium of chronic periodontitis, H413 epithelial cells derived from a human oral squamous cell carcinoma were cloned and lines expressing high levels of CD24 were selected. RNA interference protocols were designed to determine if CD24 could modulate intercellular interactions and regulate the biology of these epithelial cells. Knock-down of CD24 protein was demonstrated by Western blot and flow cytometry. The level of mRNA for CD24 was reduced 90% by RNAi treatment as assayed by real-time, reverse transcriptase (RT)-PCR. Gene products known to be important in epithelial biology, including E-cadherin and TGF-beta3 that were demonstrated to undergo altered expression patterns in the periodontal lesion, were investigated. Down-regulation of CD24 mRNA was associated with reduced e-cadherin expression and up-regulated expression of snail, twist, and tgf-beta3. The cells were treated with monoclonal antibodies to CD24 to mimic the action of auto-reactive antibodies to CD24 detected in affected patients. Relative to isotype control antibody, stimulation by anti-CD24 antibodies induced up-regulated expression of e-cadherin and down-regulation of tgf-beta3 as assessed by real-time RT-PCR. No consistent changes for expression of beta-catenin, connexins, integrins, icam-1, tgf-beta1 or tgf-beta2 were observed. CD24 could play an important role in modulating expression of genes that regulate epithelial differentiation in periodontal disease.
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PMID:Regulation of E-cadherin and TGF-beta3 expression by CD24 in cultured oral epithelial cells. 1693 May 38

The effects of growth factor loaded in nanoparticles mixed in fibrin constructs on chondrogenic differentiation were investigated by evaluating the specific cartilage extracellular matrix components in vitro and in vivo using a special cell source of bone marrow-derived stromal cells (BMSCs). The proliferation of cultured and transplanted BMSCs was found to be greater in fibrin constructs that contained TGF-beta3-loaded nanoparticles and TGF-beta3 alone than in constructs that contained unloaded nanoparticles or in fibrin hydrogel alone. Further, reverse transcriptase-polymerase chain reaction revealed that BMSCs cultured in the presence of TGF-beta3 in vitro and in vivo expressed high levels of aggrecan, cartilage oligomer matrix protein, SOX9, and type II collagen. However, a decrease in type I collagen expression was observed from 1 to 4 weeks in the presence of TGF-beta3. Moreover, histological and immunohistochemical assays revealed that large amounts of type II and proteoglycan were released from BMSCs embedded in fibrin constructs, while decreased levels of collagen type I were observed in BMSCs cultured in constructs that contained nanoparticles that were loaded with TGF-beta both in vitro and in vivo. These findings indicate that use of fibrin constructs that contained BMSCs and were provided with sustained levels of growth factors for a long period of time enabled the formation of hyaline cartilage tissue in vitro and in vivo. Overall, these results indicate that the system evaluated here may be useful for minimally invasive transplantation, BMSC differentiation, and engineering of composite tissue structures with multiple cellular phenotypes.
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PMID:In vitro and in vivo chondrogenesis of rabbit bone marrow-derived stromal cells in fibrin matrix mixed with growth factor loaded in nanoparticles. 1941 92

Iraq frequently used toxic inhalants during the war with Iran, exposing over 100,000 people to chemical reagents. Bronchiolitis obliterans (BO) is a major pulmonary disease caused by exposure to harmful gases. Recently defect in clearance of apoptotic cells (efferocytosis) has been suggested as a mechanism that leads to several lung diseases. Transforming growth factor (TGF)-beta, a cytokine produced by efferocytotic macrophages, suppresses the inflammation and enhances the regeneration of tissue. In this study, the authors compared the expression of these 3 isoforms of TGF-beta at mRNA level in lung biopsies of Iranian victims of chemical gases with lung biopsies of control healthy volunteers. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) technique was used to examine the expression level of TGF-beta isoforms using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene as an internal control. The results indicated that that levels of TGF-beta1 and TGF-beta3 mRNAs were significantly higher in chemical gas-injured patients than noninjured group (P < .05). Therefore, the authors speculate that TGF-beta1 and TGFbeta3, but not TGF-beta2, secretion is a result of efficient efferocytosis in chemically injured patients, playing a protective role by improving airway remodeling and lung homeostasis in this group. These properties of TGF-beta are consistent with long-time survival of chemical-injured people suffering from BO.
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PMID:Overexpression of transforming growth factor (TGF)-beta1 and TGF-beta3 genes in lung of toxic-inhaled patients. 2049 23


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