Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 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

Cellular disintegrin and metalloproteinases (ADAMs) are a family of genes with a sequence similar to the snake venom metalloproteinases and disintegrins. ADAMTS-1 is a unique ADAM family protein with respect to the presence of thrombospondin type I motifs and the capacity to bind to the extracellular matrix. Because ADAMTS-1 has a potential zinc-binding motif in the metalloproteinase domain, we examined in this study whether ADAMTS-1 is an active metalloproteinase by means of the proteinase trapping mechanism of alpha2-macroglobulin. We found that the soluble type of ADAMTS-1 protein is able to form a covalent-binding complex with alpha2-macroglobulin. Furthermore, the point mutation within the zinc-binding motif of ADAMTS-1 protein eliminates its capacity to bind to alpha2-macroglobulin. These data demonstrate that the metalloproteinase domain of ADAMTS-1 is catalytically active. In addition, we showed that the removal of the pro-domain from the ADAMTS-1 precursor is impaired in the furin-deficient cell line, LoVo, and that the processing ability of the cells is restored by the co-expression of the furin cDNA. These data provide evidence that the ADAMTS-1 precursor is processed in vivo by furin endopeptidase in the secretory pathway. Consequently, ADAMTS-1 is an active metalloprotease that is associated with the extracellular matrix. This study strongly suggests that ADAMTS-1 may play a role in the inflammatory process through its protease activity.
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PMID:ADAMTS-1 is an active metalloproteinase associated with the extracellular matrix. 1037

The multi-domain neutral endopeptidase, ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin repeats) is induced by parathyroid hormone (PTH) in rat osteoblasts and has therefore been suggested to be involved in initiation of bone remodeling. However, its function(s) in bone cells have not been studied. Here, we first establish that ADAMTS-1 protein is rapidly and transiently produced by human primary osteoblasts in response to PTH (1-34). We also show that ADAMTS-1 is specifically in close proximity to collagen fibrils in bone tissue using ultrastructural immunolabeling. To study the consequence(s) of ADAMTS-1 metalloprotease production in osteoblastic cells, human osteosarcoma cells (SaOS-2), were forced to express either wild-type (wtATS) or a point-mutated (pmATS) metalloprotease dead ADAMTS-1. SaOS-2 cells expressing wtATS had a growth advantage and increased collagenolytic activity when seeded inside a collagen type I gel but exhibited a reduced migration in a scratch wound assay. Immunolabeling of moving cells shows ADAMTS-1 to be located towards the direction of cellular migration. Finally, Western analysis demonstrated excess accumulation of mature collagen type I alpha1 species in the extracellular matrix together with increased release of distinct small collagen fragments into the conditioned media, by cultures of wtATS cells compared to pmATS cells. These results show that ADAMTS-1 has both the opportunity in bone and capability in vitro to induce collagen type I processing, together with a positive influence on osteoblastic three-dimensional growth. Although it is not clear at present if ADAMTS-1 promotes collagen degradation directly or indirectly, it shows that ADAMTS-1 activity can have a profound influence on the osteoblast phenotype, inhibiting migration on a planar substrate but enhancing growth in a collagen scaffold. These findings further establish ADAMTS-1 as a potentially important protein in PTH induced bone remodeling.
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PMID:ADAMTS-1 increases the three-dimensional growth of osteoblasts through type I collagen processing. 1756 Aug 40

Primary membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. Discovery of several antibodies has contributed to an increased understanding of MN. Antibodies against the M-type phospholipase A2 receptor (PLA2R) are present in 50-100% with primary MN and are associated with a lower frequency of spontaneous remission. High levels are linked with a higher probability of treatment resistance, higher proteinuria, and impaired renal function, as well as a more rapid decline of kidney function during follow-up. Immunologic remission precedes reduction of proteinuria by months. Pretransplant evaluation of PLA2R antibodies is warranted to predict recurrence of disease following renal transplantation. Several risk alleles related to the PLA2R1 gene and within the HLA loci have been identified, whereas epitope spreading of PLA2R may predict treatment response. More recently, thrombospondin type 1 domain-containing 7A (THSD7A) antibodies have been discovered in primary MN. Several other rare antigens have been described, including antibodies against neutral endopeptidase as a cause of antenatal MN and circulating cationic bovine serum albumin as an antigen with implications in childhood MN. This review focuses on the progress with a special focus on diagnostic accuracy, predictive value, and treatment implications of the established and proposed antigens.
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PMID:Recent Progress in Deciphering the Etiopathogenesis of Primary Membranous Nephropathy. 2890 48

Membranous nephropathy is a noninflammatory autoimmune disease of the kidney glomerulus, characterized by the formation of immune deposits, complement-mediated proteinuria, and risk of renal failure. Considerable advances in understanding the molecular pathogenesis have occurred with the identification of several antigens [neutral endopeptidase, phospholipase A2 receptor (PLA2R), thrombospondin domain-containing 7A (THSD7A)] in cases arising from the neonatal period to adulthood and the characterization of antibody-binding domains (that is, epitopes). Immunization against PLA2R occurs in 70% to 80% of adult cases. The development of highly specific and sensitive assays of circulating antibodies has induced a paradigm shift in diagnosis and treatment monitoring. In addition, several interacting loci in HLA-DQ, HLA-DR, and PLA2R1, as well as classical human leukocyte antigen (HLA)-D alleles have been identified as being risk factors, depending on a patient's ethnicity. Additionally, mechanisms of antibody pathogenicity and pathways of complement activation are now better understood. Further research is mandatory for designing new therapeutic strategies, including the identifying triggering events, the molecular bases of remission and progression, and the T cell epitopes involved.
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PMID:Molecular Pathogenesis of Membranous Nephropathy. 3162 60