Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extractable nuclear antigen (ENA) is composed of at least two components, one a ribonucleo-protein sensitive to ribonuclease or heat and the other a protein. Antibodies to ENA are associated with a relatively benign clinical course in patients with systemic lupus erythematosus (SLE) in which DNA anti DNA complexes are thought pathogenic. The effect of ENA and anti-ENA on DNA anti-DNA reactions in vitro was studied. ENA effectively inhibited an anti-DNA hemagglutination reaction but no effect was found on binding of radioactive DNA or on the anti-hemocyanin hemagglutination reaction. The inhibitory effect was not abolished by yeast ribonuclease (RNase), heating, or DNase. Anti-ENA HAD NO EFFECT ON ANTI-DNA hemagglutination. In vivo, ENA altered the NZB/NZW mouse nephritis thought to be a model for human SLE nephritis. These results suggest the possiblity of a role for ENA in alteration of diseases due to pathogenic DNA anti-DNA complexes.
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PMID:Extractable nuclear antigen effect on the DNA anti-DNA reaction and NZB/NZW mouse nephritis. 107 29

Forty-four patients with antibodies to ribonuclease-sensitive extractable nuclear antigen (ENA), ribonuclease-resistant ENA, or both, are described. Most patients with antiribonucleoprotein (anti-RNP) antibodies have overlapping features of systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), and polymyositis, and have a low incidence of nephritis. Most patients with antibody solely to ribonuclease-insensitive ENA have SLE; these patients with SLE are typical of the general SLE population, except that they demonstrate an increased incidence of Raynaud phenomenon. Furthermore, it is shown that antibody to ENA may occur in other rheumatic and nonrheumatic diseases, and that not all patients who have a clinical overlap of SLE and PSS that is suggestive of mixed connective tissue disease have anti-RNP antibody.
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PMID:Antibodies to components of extractable nuclear antigen. Clinical characteristics of patients. 108 22

Fibronectin: (FNs) comprise a family of adhesive glycoproteins that are prominent components of mesangial extracellular matrix and accumulate during glomerular injury. By alternative splicing of an unique mRNA precursor, various FN isoforms can be originated. In rat, three regions of the molecule are involved: EIIIA, EIIIB and V. Because specific FN isoforms are expressed in embryogenesis and wound healing, conditions characterized by cell migration and adhesion, we examined the pattern of FN isoforms in the mild and severe phases of a progressive immune complex proliferative nephritis in rats. We constructed specific probes to analyze the splicing pattern of FN pre-mRNAs by ribonuclease protection assays. FN mRNAs containing EIIIA, EIIIB and V regions increased along, the progression of nephritis, though the increment of EIIIB-FN mRNA was modest. However, different regulation of all these isoforms was observed. The percentage of FN mRNA containing the EIIIA exon versus total FN increased with the severity of the disease, while the percentage of FN mRNA containing the EIIIB exon decreased. Relative V-FN mRNA expression versus total FN mRNA increased only in the severe phase. By means of specific antibodies we also studied the presence of EIIIA, EIIIB and V-FN proteins in the kidney. In the normal glomerutus, EIIIA-FN protein was barely detectable in the mesangium, increasing in the mild phase of nephritis. In the severe phase of nephritis, increased EIIIA-FN was localized in the mesangium, in Bowman's capsule and in crescents. By contrast, EIIIB-FN protein in the glomerulus was absent even in the severe phase. V120-FN protein, an isoform that mediates the attachment of leukocytes through the VLA-4 integrin, was present in the mesangium and glomerular capillary loops in control animals, and increased in the severe phase of nephritis, coinciding with a strong leukocyte infiltration. In conclusion, our results show that during immune glomerular injury there were marked changes in the pattern of FN isoforms expression. Since those isoforms, particularly V120 isoform, are important in cell adhesion and migration, their up-regulation may facilitate the recruitment of cells into the injured glomeruli. The blockade of the interaction between V120-FN and infiltrating leukocytes may represent a new approach to the treatment of nephritis.
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PMID:Glomerular up-regulation of EIIIA and V120 fibronectin isoforms in proliferative immune complex nephritis. 887 66

Fibronectins (FN) regulate cell migration, proliferation, and matrix formation during tissue injury. In humans, up to 20 different FN isoforms are generated by alternative splicing in three regions called EIIIA, EIIIB, and V, which have been implicated in the process undergoing wound healing and embryonic development. Specifically, EIIIA- and EIIIB-containing isoforms have been implicated in the regulation of cell proliferation and migration, whereas FN isoforms containing the full-length V region (named V120) are ligands to the VLA-4 integrin. To study the changes in the expression of FN isoforms in the anti-Thy-1 nephritis, an acute and self-resolutive model of mesangioproliferative nephritis, we analyzed the FN splicing patterns by means of ribonuclease protection assays. At Day 7 after anti-Thy-1 monoclonal injection, time of the maximal matrix expansion and glomerular hypercellularity, EIIIA+, EIIIB-, and V120 FN mRNA isoforms were increased. In accordance with the mRNA studies, FN proteins, including the EIIIA and V120 regions, increased in the mesangium of nephritic rats, as assayed by immunohistochemistry. Coinciding with the EIIIA and V120 isoforms up-regulation, there was an increase in mesangial cell proliferation and in the number of VLA-4+ infiltrating cells. At Day 14, in parallel with a remission of the above-mentioned changes, there was a decline in the mRNA and protein FN isoforms increased in the previous phase. The marked and reversible changes in the pattern of FN isoforms and their temporal association with other indicators of glomerular injury suggest that certain FN isotypes are important and coordinated components of the mechanisms attempting to reverse glomerular damage.
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PMID:Changes in the pattern of fibronectin mRNA alternative splicing in acute experimental mesangioproliferative nephritis. 1006 6

Anti-glomerular basement membrane (GBM) nephritis in Sprague-Dawley (SD) rats was characterized by development of marked glomerular sclerosis and tubulointerstitial fibrosis. To elucidate sequential change of the glomerular sclerosis and tubulointerstitial fibrosis, accumulation and mRNA expression of extracellular matrix (ECM) components and transforming growth factor (TGF)-beta were examined in the glomerulus and cortex during the disease course by histology, immunostaining and ribonuclease protection assay. Mild proliferative and degenerative lesions appeared in the glomeruli by day 15 after anti-GBM antibody binding to GBM and progressed to glomerular sclerotic lesion thereafter. Conversely, interstitial change was first recognized by infiltration of mononuclear cells after day 20, followed by marked accumulation of ECM and tubular degeneration. The interstitial fibrosis was induced without apparent binding of anti-GBM antibody to tubular basement membrane. Accumulation of fibronectin, collagen type I and type IV was noted in the interstitium by immunofluorescence microscopy in association with enhanced expression of mRNA for these ECM components and their regulatory molecules such as matrix metalloproteinase (MMP2), tissue inhibitor of metalloproteinase (TIMP)-1 and TGF-beta1 both in glomeruli and cortex. The glomerular expression of these mRNA increased apparently by day 15 and reached a plateau or a peak at day 20. The expression of the same mRNA increased gradually from day 15 to day 29 in the cortex. These observations show that interstitial fibrosis follows glomerular sclerosis after anti-GBM antibody injection in SD rats, suggesting that at least a part of the mechanism for ECM accumulation in the glomerulus and interstitium is essentially the same in terms of composition of ECM and expression of its regulatory molecules.
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PMID:Expression profile of extracellular matrix and its regulatory proteins during the process of interstitial fibrosis after anti-glomerular basement membrane antibody-induced glomerular sclerosis in Sprague-Dawley rats. 1050 39