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)

To study the differential expression of the murine VLA-4 (alpha 4 beta 1) integrin, the 5'-flanking region of the gene for the alpha subunit (alpha 4m) was isolated and a cDNA for alpha 4m was obtained with reverse transcriptase polymerase chain reaction (RT-PCR). The cDNA sequence contained a difference in the signal peptide region compared to the previously described cDNA (Neuhaus et al., 1991). As a consequence, another start codon is predicted, resulting in a decrease in size of the signal peptide. This was confirmed by genomic sequencing. The promoter region was delimited by ribonuclease protection assay (RPA) and transfection experiments fusing 5'-upstream fragments to the luciferase gene. A fragment extending from -936 to +221 was capable of controlling the expected cell-type-specific expression. Sequence comparison of the mouse alpha 4m promoter region with the human alpha 4h promoter revealed little homology. Like most integrin subunits, alpha 4m lacks TATA anc CCAAT boxes. Putative recognition sites for DNA-binding nuclear factors (AP1, AP2, Sp1, and PU1) were identified. The characterization of the promoter region and further identification of the transcription regulatory elements should provide insight in the regulation of alpha 4m integrin gene expression.
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PMID:Cloning and characterization of the promoter region of the murine alpha-4 integrin subunit. 777 55

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