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)

A panel of cell-type specific monoclonal and polyclonal antibodies and lectins was used to examine the early, morphologically epithelial outgrowth of rat renal glomerular cells in culture. The cell type-specific reactivity of the monoclonal antibodies has been previously verified on tissue sections of rat kidneys at light and electron microscopic levels. Morphologically distinct epithelial cells grew out from the isolated glomeruli within 3 days in culture, followed by the growth of morphologically typical stellate mesangial-like cells. Endothelial and mesangial cells were positively identified from the early cultures (up to 10 days) with antibodies to a 350 kD protein, dipeptidyl peptidase IV, podocalyxin, factor VIII, OX-43 and with Bandeiraea simplicifolia (BS-I B4) lectin, and with antibodies to smooth muscle actin, desmin, Thy1.1 antigens and with Ricinus communis (RCA-1) lectin, respectively. The antibodies recognizing podocytes in vivo (antipodocalyxin, anti-O-acetyl GD3 ganglioside, anti-gp330, anti-C3b complement receptor, anti-vimentin and anti-CALLA) consistently failed to bind to the predominant epithelial cells in early cultures, although these antibodies readily bound to the cells of the intact glomeruli remaining in culture. The attempts to augment the expression of cell-type specific epitopes by culturing glomeruli on various matrices or by enriching the medium with various growth factors, failed to induce podocytic epitopes on the growing epithelial cells. Glomeruli from newborn rats cultured in vitro, but were also constantly negative for the markers of podocytes. In addition, we cultured glomerular-like bodies from in vitro were induced metanephric mesenchymes but failed to obtain evidence of growing podocytes. However, the epithelial cells reacted with antibodies to thrombospondin and cytokeratin that react with the parietal epithelium of glomeruli on tissue sections. The results show that early glomerular cultures consist of mesangial, endothelial and presumably parietal epithelial cells readily identifiable by immunocytochemical methods. No podocytes could be grown under the various growth conditions tested. This suggests that glomerular podocytes are effectively growth arrested and call for new approaches to obtain these cells in culture.
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PMID:Rat glomerular cells do not express podocytic markers when cultured in vitro. 175 4

Mesangial cell proliferation is a common cellular response to a variety of different types of glomerular injury. Complement C5b-9 is a prime candidate to mediate mesangial cell proliferation, especially sublytic C5b-9, which can induce the production of multiple inflammatory factors and cytokines. Transforming growth factor (TGF)-beta1 plays a major role in the accumulation of extracellular matrix (ECM), while thrombospondin (TSP)-1 has been identified as an activator of latent TGF-beta1 in an in vitro system. Using rat glomerular mesangial cells (GMCs) as a model system, we assessed the effect of sublytic C5b-9 on the expression of TSP-1 and TGF-beta1 and explored the relevant pathway of signal transduction. First, we ensured the concentrations of anti-Thy1 antibody and complement, which were regarded as a sublytic C5b-9 dose, and examined whether the sublytic C5b-9 induced expression of TSP-1 in rat GMCs which, in turn, activated latent TGF-beta1 by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Then, we investigated the role of the PI3-k/Akt pathway in sublytic C5b-9-induced TSP-1 production in rat GMCs by Western blot analysis. The addition of sublytic C5b-9 (5% anti-Thy1 antibody and 4% normal serum) to rat GMCs induced activation of latent TGF-beta1 via TSP-1. The addition of sublytic C5b-9 apparently increased the protein of Akt phosphorylation, whereas PI3-k inhibitor LY294002 could clearly reduce the increase of TSP-1 induced by sublytic C5b-9. These results indicate that TSP-1 is an activator of latent TGF-beta1 in sublytic C5b-9-induced rat GMCs; furthermore, the PI3-k/Akt signal transduction pathway may play a key role in sublytic C5b-9-induced TSP-1 production.
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PMID:Sublytic complement C5b-9 complexes induce thrombospondin-1 production in rat glomerular mesangial cells via PI3-k/Akt: association with activation of latent transforming growth factor-beta1. 1663 7

We recently identified thrombospondin-2 (TSP-2) as an endogenous regulator of matrix remodelling and inflammation in experimental kidney disease by studying TSP-2-deficient mice. In this study, we asked whether systemic TSP-2 overexpression via thigh muscle transfection is able to ameliorate the time course of the anti-Thy1 glomerulonephritis model. After induction of anti-Thy1 nephritis, rats were transfected either with an overexpression plasmid for TSP-2 or lacZ as a control. Biopsies, urine, and blood samples were taken on days 1, 3, and 6 after disease induction. Muscular overexpression of TSP-2 reduced glomerular transforming growth factor (TGF)-beta activation and glomerular extracellular matrix formation as determined by collagen IV and fibronectin. In addition, activation of mesangial cells to the myofibroblast-like phenotype was also significantly decreased in TSP-2-overexpressing animals. TSP-2 overexpression inhibited both glomerular endothelial and mesangial cell proliferation, resulting in a reduced glomerular cell number and glomerular tuft area. The inflammatory response, as monitored by T cells and antigen-presenting cells, was reduced significantly by TSP-2 overexpression, but influx of macrophages was unchanged. These data demonstrate TSP-2 as a potential therapeutic agent to inhibit the glomerular proliferative and inflammatory response as well as TGF-beta activation and extracellular matrix accumulation in experimental mesangial proliferative glomerulonephritis.
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PMID:Thrombospondin-2 therapy ameliorates experimental glomerulonephritis via inhibition of cell proliferation, inflammation, and TGF-beta activation. 1972 47