Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Suspension and attachment cultures of Y79 human retinoblastoma cells were treated with all-trans retinoic acid (RA) for up to 10 days to assess its effect on growth and cell-surface expression of immunoglobulin superfamily antigens MHC class I and class II, ICAM-1, NCAM and Thy1. RA up to 10 microM induced growth inhibition, and marked morphological differentiation with extension of prominent processes resembling neurites was seen in attachment cultures. However, above 10 microM RA produced extensive cell death. We also observed increased cell-surface expression of MHC class I, ICAM-1, NCAM and Thy1 on Y79 cells treated with 10 microM over 10 days; constitutive MHC class II expression was not apparent, nor did RA treatment appear to induce Y79 cells to express MHC class immunoreactivity. The up-modulation of cell-adhesion molecules (NCAM, ICAM-1 and Thy1) and immune recognition molecules (NCAM, ICAM-1 and MHC class I), associated with reduced growth and tumour cell differentiation, suggests that RA may have a potential role in regulating the growth and development of retinoblastoma tumours.
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PMID:Human retinoblastoma: in vitro differentiation and immunoglobulin superfamily antigen modulation by retinoic acid. 922 76

We studied the expression of the NO synthase isoforms in an in vitro model of neural development using RT-PCR, Western blot and immunohistochemistry. Murine PCC7-Mz1 cells (Jostock et al., Eur. J. Cell Biol. 76, 63-76, 1998) differentiate in the presence of all-trans retinoic acid and dibutyryl cAMP along the neural pathway into neuron-like, fibroblast-like and astroglia-like cells. Undifferentiated cells showed immunofluorescent staining for neuronal-type NOS I and endothelial-type NOS III. This expression pattern was retained in those cells differentiating into neurofilament- and tau protein-positive neuronal cells. Thymocyte alloantigen (Thy1.2/CD 90.2)-positive fibroblasts, appearing around day 3, and glial fibrillary acidic protein (GFAP)-positive astroglial cells, appearing after day 6 of differentiation, stained negative for any NOS isoform. Starting at day 6 of differentiation, expression of inducible-type NOS II could be stimulated with cytokines in a subset of cells, which may represent activated astrocytes. NOS II was always undetectable in non-induced cultures. These data indicate that the ability of stem cells to express NOS I and NOS III is only retained when the cells differentiate along the neuronal lineage, while a small subpopulation of cells acquires the ability to express NOS II in response to cytokines.
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PMID:Analysis of NO synthase expression in neuronal, astroglial and fibroblast-like derivatives differentiating from PCC7-Mz1 embryonic carcinoma cells. 1009 36

ABSTRACT.: In the reaction of kidneys to injury, cytokine-driven proliferation plays an important role and precedes the development of glomerulosclerosis. There is great interest in agents that may interfere with such proliferation. Therefore, a rat model of mesangioproliferative glomerulonephritis (induced by anti-Thy1.1) was studied, and the effects of all-trans-retinoic acid (all-trans-RA) and isotretinoin, powerful antiproliferative and anti-inflammatory substances, on glomerular damage and cell proliferation were examined. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans-RA or 40 mg/kg body wt isotretinoin (n = 9 to 11 per group), using either a pretreatment (days -2 through 8) or posttreatment (days +3 through +8) protocol, i.e., starting before or after the induction of anti-Thy1.1 nephritis, respectively. All-trans-RA prevented the BP increase evoked by anti-Thy1.1 (anti-Thy1.1/vehicle, 112.2 +/- 4.8 mmHg; anti-Thy1.1/RA, 87.5 +/- 2. 5 mmHg; P < 0.001). Treatment with all-trans-RA or isotretinoin produced a 70% decrease in the urinary albumin excretion rate (P < 0. 02). Periodic acid-Schiff staining of saline-perfused kidneys (day 8) revealed significantly fewer glomerular cells in RA-treated nephritic rats (anti-Thy1.1/vehicle, 97 +/- 3.1 cells/glomerulus; anti-Thy1.1/RA, 80 +/- 4.4; P < 0.02; control/vehicle, 69 +/- 1.2). No difference was observed between all-trans-RA and isotretinoin treatment. The capillary occlusion scores were significantly lower for the anti-Thy1.1/RA-treated group (1.9 +/- 0.1) than for the anti-Thy1.1/vehicle-treated group (2.9 +/- 0.5, P < 0.001). In the anti-Thy1.1/vehicle-treated group, 11.9 +/- 1.1 glomerular cells were proliferating cell nuclear antigen-positive; however, in the anti-Thy1.1/RA-treated group, only 5.3 +/- 0.8 cells were proliferating cell nuclear antigen-positive (P < 0.002; control, 2.2 +/- 0.2). Glomerular mitoses were reduced by 67% in the anti-Thy1. 1/RA-treated group, compared with the anti-Thy1.1/control group (P < 0.002). Glomerular staining for platelet-derived growth factor B-chain was significantly reduced in anti-Thy1.1-treated nephritic rats in the presence of isotretinoin or all-trans-RA, compared with the vehicle-treated group (P < 0.001). It is concluded that all-trans-RA limits glomerular proliferation, glomerular lesions, and albuminuria in an established model of renal damage. The findings point to retinoids as potential novel modulators of glomerular injury.
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PMID:Retinoic acid reduces glomerular injury in a rat model of glomerular damage. 1090 61

We previously demonstrated that all-trans retinoic acid (RA) preserves glomerular structure and function in anti-Thy1.1 nephritis (Wagner J, Dechow C, Morath C, Lehrke I, Amann K, Floege J, and Ritz E. J Am Soc Nephrol 11: 1479-1489, 2000). Because the renin-angiotensin system (RAS) contributes to renal damage, we 1) studied retinoid-specific effects on its components and 2) compared the effects of all-trans-RA with those of the AT(1)-receptor blocker candesartan. Rats were pretreated for 3 days before injection of the OX-7 antibody and continued with treatment with either vehicle or daily injections of 10 mg/kg all-trans-RA only (study 1) or 10 mg/kg body wt all-trans-RA, 1 mg/kg candesartan, or both (study 2) for an additional 7 days. The blood pressure increase observed in anti-Thy1.1 nephritic rats was equally normalized by all-trans-RA and candesartan (P < 0.05). In nephritic rats, mRNAs of angiotensinogen and angiotensin-converting enzyme (ACE) in the kidney were unchanged, but renin mRNA was lower (P < 0.01). Renal and glomerular AT(1)-receptor gene and protein expression levels were higher in anti-Thy1.1 nephritic rats (P < 0.05). In the renal cortex of nephritic rats, pretreatment with all-trans-RA significantly reduced mRNAs of all the examined RAS components, but in the glomeruli it increased ACE gene and protein expression (P < 0.01). In nephritic rats, candesartan reduced the number of glomerular cells and mitoses (P < 0.05) less efficiently than all-trans-RA (P < 0.01). Both substances reduced cellular proliferation (proliferating cell nuclear antigen) significantly (P < 0.05). No additive effects were noted when both compounds were combined. In conclusion, all-trans-RA influences the renal RAS in anti-Thy1.1 nephritis by decreasing ANG II synthesis and receptor expression. The beneficial effect of retinoids may be explained, at least in part, by reduction of RAS activity.
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PMID:Effects of all-trans retinoic acid on renin-angiotensin system in rats with experimental nephritis. 1159 49

Transforming growth factor-beta1 (TGF-beta 1) overexpression plays a key role in the glomerular accumulation of extracellular matrix proteins in renal disease. Retinoids have previously been shown to significantly limit glomerular damage in rat experimental glomerulonephritis. Therefore, the effects of all-trans retinoic acid and isotretinoin on the components of the TGF-beta system and extracellular matrix proteins in anti-Thy1.1-nephritis (Thy-GN) were investigated. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans retinoic acid or 40 mg/kg body wt isotretinoin (n = 9 per group) either with a pretreatment (day -2 through 8) or posttreatment protocol (day +3 through 8), i.e., starting before or after induction of Thy-GN, respectively. Urinary TGF-beta 1 excretion was 60% lower in all-trans retinoic acid-treated animals with Thy-GN (P < 0.025). The increase of cortical TGF-beta 1 gene expression in Thy-GN rats was significantly attenuated with all-trans retinoic acid and even more with isotretinoin treatment as compared with untreated animals (P < 0.025). Cortical expression of TGF receptor II, but not receptor I gene expression, was significantly lower in animals treated with all-trans retinoic acid or isotretinoin (P < 0.05). In all-trans retinoic acid-treated animals with Thy-GN, the increase of glomerular TGF-beta 1 protein (P < 0.008) and TGF-beta 1 (P < 0.025) and TGF receptor II mRNA (P < 0.015) was significantly less. Immunohistochemistry revealed less glomerular staining for TGF-beta 1 and TGF receptor II in the presence of all-trans retinoic acid. TGF-beta 1 immunostaining was not restricted to monocytes and macrophages, as indicated by double-staining. Glomerular staining for collagen IV and collagen III was less in animals treated with isotretinoin (P < 0.02 for both) in contrast to all-trans retinoic acid, whereas fibronectin remained unchanged. It was concluded that the beneficial effects of retinoids on glomerular damage are presumably due to a marked reduction in renal TGF-beta 1 and TGF receptor II expression.
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PMID:Effects of retinoids on the TGF-beta system and extracellular matrix in experimental glomerulonephritis. 1167 6

Retinoids are potent antiproliferative and anti-inflammatory compounds. We previously demonstrated that the natural pan-agonists all-trans retinoic acid (RA) and 13-cis RA efficiently preserve renal structure and function in rat mesangioproliferative glomerulonephritis. We examine effects of synthetic retinoid receptor-specific agonists 1) to identify common and receptor subtype-specific pathways in this model and 2) to characterize effects of retinoids on the renal endothelin (ET) system. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of agonists specific for retinoid A (Ro-137410) and retinoid X (Ro-257386) receptors and the complex anti-activator protein-1 active retinoid BMS-453 7 days after induction of anti-Thy1.1 nephritis (n = 7-9/group). The different retinoids lowered glomerular ET-1 and ET type A and B receptor gene expression in control and nephritic rats with comparable efficacy. Reduction of glomerular c-Fos and GATA-2 mRNA expression levels suggests downregulation of transcription factors required for ET expression. The different retinoids were similar in their action on the glomerular capillary occlusion score, number of total glomerular cells, and glomerular infiltrating macrophage count. They differed in their ability to normalize blood pressure (Ro-257386 > BMS-453 > arotinoid), albuminuria (BMS-453 > Ro-257386 > arotinoid), and creatinine clearance (arotinoid > BMS-453 > Ro-257386). No signs of toxicity were observed. We conclude that all retinoid agonists with different subtype specificity are highly efficient in reducing renal damage and proliferation of mesangial cells. Retinoid X and A receptor-specific pathways are apparently involved in the antiproliferative, anti-inflammatory, and anti-ET action. Further studies are indicated to define the potential use of retinoid agonists in inflammatory renal disease.
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PMID:Retinoid receptor-specific agonists alleviate experimental glomerulonephritis. 1188 Mar 36

Cytokine-driven proliferation and inflammation play important roles in the response of the kidney to injury and precede the development of glomerulosclerosis. There is great interest in agents which may interfere with such proliferation and inflammation. Therefore, a rat model of mesangioproliferative glomerulonephritis was studied and the effects of all-trans retinoid acid (RA) and isotretinoin, powerful anti-proliferative and anti-inflammatory substances, on glomerular damage and cell proliferation were examined. The use of retinoids was also warranted because of their known (suppressive) effects on genes involved in the pathogenesis of renal damage. RA prevented the blood pressure increase evoked by anti-Thy1.1 nephritis. Treatment with either RA or isotretinoin reduced the albumin excretion rate by 70%. Periodic acid-Schiff (PAS) stains revealed significantly fewer glomerular cells in nephritic rats treated with retinoids. Similarly, the number of mitoses and of cells which stained positively for proliferating cell nuclear antigen was significantly less in nephritic glomeruli treated with retinoids compared with the vehicle-treated group. Glomerular expression of platelet-derived growth factor B-chain was significantly reduced in the presence of retinoids. It was concluded that retinoids limit glomerular proliferation, glomerular lesions and albuminuria in an established model of renal damage. These findings point to retinoids as potential novel modulators of glomerular injury.
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PMID:Nuclear (receptor) power: retinoids in rat mesangioproliferative disease. 1238 99