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)

Studies have shown that lipoxin A(4) (LXA(4)) inhibited proliferation of mesangial cells in vitro induced by platelet-derived growth factor, epidermal growth factor, leukotriene D(4) or tumor necrosis factor-alpha. In this study, we investigated the protective effects of 15(R/S)-methyl-LXA(4) on mesangioproliferative nephritis in rats and the signal transduction involved in actions of 15(R/S)-methyl-LXA(4). Mesangioproliferative nephritis was induced by a single intravenous injection of the mouse monoclonal anti-Thy1.1 antibodies. The nephritic rats were treated by intravenous injection of 15(R/S)-methyl-LXA(4) every 8h until the rats were sacrificed. There were increments in glomerular infiltration of leukocytes, expressions of protein and mRNA of interleukin (IL)-1beta and IL-6, activities of nuclear factor-kappaB (NF-kappaB) in nephritic rats from day 1 to 4 after induction of nephritis. The enhanced proteinuria, proliferation score of mesangial cells, glomerular proliferating cell nuclear antigen (PCNA) positive cells, activities of phosphorylated phosphoinositide 3-kinase (PI3-K), Akt(1), alpha-smooth muscle actin (alpha-SMA) and signal transducer and activator of transcription 3(STAT(3)), and reduced expression of p27(kip1) were found on day 4 after induction of nephritis. Treatment of nephritic rats with 15(R/S)-methyl-LXA(4) significantly reduced the protenuria, glomerular infiltration of leukocyte, expressions of protein and mRNA of IL-1beta and IL-6, proliferation score of mesangial cells, glomerular PCNA positive cells, activities of phosphorylated PI3-K, Akt(1), alpha-SMA, NF-kappaB and STAT(3), and ameliorated the decrement in p27(kip1) induced by anti-Thy1.1 antibodies. Protective effects of 15(R/S)-methyl-LXA(4) on nephritis induced by anti-Thy1.1 antibodies were related to PI3-K/Akt(1)/p27(kip1)/cyclin pathway, STAT(3) and NF-kappaB pathway-dependent signal transduction.
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PMID:Signal transduction involved in protective effects of 15(R/S)-methyl- lipoxin A(4) on mesangioproliferative nephritis in rats. 1732 90

Glomerular mesangial cells (MCs) proliferate and produce extracellular matrix proteins in many progressive renal diseases. Recently, histone deacetylase inhibitors (HDIs) were shown to have antiproliferative and antifibrogenic effects in some in vitro and in vivo models. Using the [(3)H]-thymidine incorporation test, we have found that the HDI trichostatin A (TSA) effectively inhibits MC growth at nontoxic nanomolar concentrations. Similarly, the HDI valproic acid also inhibited MCs proliferation. Cell-cycle analysis indicated an arrest in G(0)/G(1) phase in response to TSA, which was accompanied by elevation in synthesis of the cyclin-dependent kinase inhibitors (CDKIs) p21/Waf1 and p27/Kip1. TSA treatment suppressed alpha-smooth muscle actin, transforming growth factor-beta1, and collagen protein synthesis by MCs and induced myofibroblast-like appearance of proliferating MCs. In the in vivo model of the anti-Thy1.1-induced glomerulonephritis, TSA and valproic acid treatments significantly suppressed proteinuria. Collectively, these data suggest a therapeutic potential for HDIs in the treatment of mesangial proliferative diseases and glomerulosclerosis.
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PMID:Effects of histone deacetylase inhibitors on rat mesangial cells. 1992 17

Over proliferation of glomerular mesangial cells (MCs) disturbs mesangial homeostasis and leads to renal damage in mesangioproliferative glomerulonephritis. It is documented that transcriptional factors may be involved in the proliferation of MCs. This study aims to identify the key transcriptional factor that prevents the MCs from over proliferation and to clarify its regulatory mechanism. Microarray analysis of glomeruli isolated from Sprague-Dawley rats (SD rats) with or without anti-Thy1 nephritis (anti-Thy1N) showed that the cell cycle pathway was the most enriched pathway in anti-Thy1N model, and the D-site binding protein (DBP) ranked first in the cluster of transcription factors. Compare with normal rats, DBP is markedly decreased accompanied by an over proliferation of MCs in rats with anti-Thy1N. The cell proliferative capacity was measured by 5-Ethynyl-2'-deoxyuridine (EdU) assay in primary rat MCs with DBP knockdown or overexpression, respectively. The results showed that the knockdown of DBP significantly promoted the proliferation of MCs, whereas the overexpression of DBP inhibited the MCs' proliferation, compared to that of the control cells. Further study indicated that DBP arrested G1/S-phase transition by inhibiting the expression of p21, p27 and inducing the Cyclin D1 expression in MCs. The current data suggest that DBP effectively inhibits the proliferation of MCs through G1 phase arrest, and the decrease of DBP may induce mesangial over proliferation in rats with anti-Thy1N.
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PMID:D-site binding protein regulates cell proliferation through mediating cell cycle progression in rat mesangial cells. 3175 5