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)

It has been demonstrated in anti-Thy1 glomerulonephritis that extracellular adenine nucleotides have a significant pro-inflammatory activity, however, glomerular ATP/ADPase, which in concert with 5'-nucleotidase converts ATP/ADP, and AMP to anti-inflammatory adenosine had an anti-inflammatory role. We have studied distribution of 5'-nucleotidase and divalent cation-activated ATPase in kidney biopsies of 15 patients with glomerulonephritis. The major finding was an overexpression of 5'-nucleotidase in the mesangium of kidney from patients with membranous nephropathy. No change in 5'-nucleotidase expression was observed in other common forms of glomerulonephritis: IgA nephropathy, mesangioproliferative and mesangiocapillary glomerulonephritis. The distribution of Mg(2+)-ATPase in investigated specimens was similar to control distribution. Results obtained in this study indicate increased mesangial expression of 5'-nucleotidase in non-proliferative form of glomerulonephritis consistent to a role of mesangial cells in inflammatory processes.
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PMID:Increased expression of glomerular mesangial cell 5'-nucleotidase in membranous nephropathy. 1218 7

Increased glomerular prostaglandin E(2) (PGE(2)) production is associated with the progression of diseases such as membranous nephropathy, nephrotic syndrome, and anti-Thy1 nephritis. We investigated the signaling pathways that regulate the synthesis and actions of PGE(2) in glomerular podocytes. To study its actions, we assessed the ability of PGE(2) to regulate the production of its own precursor, arachidonic acid (AA), in a mouse podocyte cell line. PGE(2) dose-dependently reduced phorbol ester (PMA)-mediated AA release. Inhibition of PMA-stimulated AA release by PGE(2) was found to be cAMP/PKA-dependent, because PGE(2) significantly increased levels of this second messenger, whereas the inhibitory actions of PGE(2) were reversed by PKA inhibition and reproduced by the cAMP-elevating agents forskolin and IBMX. PGE(2) synthesis in this podocyte cell line increased fourfold at 60 min in response to PMA, coinciding with upregulation of cyclooxygenase (COX)-2 but not COX-1 levels. However, PGE(2) synthesis was significantly reduced by COX-1-selective inhibition, yet to a lesser extent by COX-2-selective inhibition. Our findings suggest that PMA-stimulated PGE(2) synthesis in mouse podocytes requires both basal COX-1 activity and induced COX-2 expression, and that PGE(2) reduces PMA-stimulated AA release in a cAMP/PKA-dependent manner. Such an autocrine regulatory loop might have important consequences for podocyte and glomerular function in the context of renal diseases involving PGE(2) synthesis.
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PMID:PGE2 reduces arachidonic acid release in murine podocytes: evidence for an autocrine feedback loop. 1238

Membranous nephropathy is an autoimmune-mediated glomerulonephritis and a major cause of nephrotic syndrome. We studied the kinetics of adaptive immunity in the pathogenesis of membranous nephropathy in T1/T2 double transgenic mice (T1/T2 TG mice) that express human Thy1 protein under the control of interferon-gamma (INF-gamma) and mouse Thy1.1 protein under the control of interleukin (IL)-4. Nephropathy was induced by cationic bovine serum albumin. We found that splenocytes expressed a progressive Th2 response and a subsequent compensatory T-helper 1 (Th1) response, with a gradual augmentation of IL-4-producing Th2 cells and INF-gamma-producing Th1 cells. Increased Th2 marker expression was seen in peripheral blood and kidney cells, with the immunoglobulin G1 (IgG1) antibody isotype predominant in the serum and kidneys. We found that CD8+ T cells contribute more to the augmented INF-gamma production than CD4+ T cells. Moreover, CD19+ B cells demonstrated a greater production of IL-4 than the CD4+ T cells. Cytokine-related gene expression in kidneys and splenocytes showed an upregulation of proinflammatory Th1 and Th2 cytokines. Th2 cells but not Th1 cells were significantly correlated with serum cholesterol and proteinuria. Our study shows that both peripheral and renal immune reactions are strongly polarized toward Th2-type immune responses during the course of membranous nephropathy. The T1/T2 mouse model may help decipher the kinetic changes of adaptive immunity in glomerulonephritis.
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PMID:Kinetics of adaptive immunity to cationic bovine serum albumin-induced membranous nephropathy. 1762 71