Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) stimulates cell migration, proliferation and the formation of tube-like structures of human microvascular endothelial cells in culture. Heparin-binding EGF-like growth factor(HB-EGF), which shows 35% homology with EGF/TGF-alpha, is a member of the EGF family, and it is ubiquitous in many tissues and organs. We examined whether or not HB-EGF induced angiogenic responses in human microvascular endothelial cells. HB-EGF inhibited the binding of (125) I-EGF to the EGF receptor and induced autophosphorylation of the receptor on endothelial cells. Exogenous HB-EGF induced the loss of more than 70% of the EGF receptor from the cell surface within 30 min, with similar kinetics to that of EGF. The level of c-fos mRNA markedly increased at 30 min in response to HB-EGF as well as EGF. A gel shift assay demonstrated the activation of the transcription factor p91 by HB-EGF and EGF. This factor directly interacts with EGF receptor and mediates the activation of c-fos gene promoter. HB-EGF enhanced the mRNA expression of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) mRNA. However, the enhancement of t-PA and PAI-1 by HB-EGF was less than that by EGF. Heparitinase/chlorate, which digests the heparan sulfate proteoglycan of the endothelial cell surface, restored both t-PA and PAI-1 mRNA levels in response to HB-EGF in a manner similar to that by EGF. HB-EGF at 10 ng/ml developed tube-like structures in type I collagen gel at similar levels to that of EGF at 10 ng/ml, suggesting that HB-EGF is also a potent angiogenic factor in the model system for angiogenesis. The tubulogenesis activity of HB-EGF is discussed in relation to the expression of the t-PA and PAI-1 genes.
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PMID:Heparin-binding epidermal growth factor-like growth factor: p91 activation induction of plasminogen activator/inhibitor, and tubular morphogenesis in human microvascular endothelial cells. 860 52

Alterations of the host response by tobacco smoke adversely affect the periodontium. In this study, we examined the effects of in vitro acute smoke exposure on changes in m-RNA expression of primary peripheral mononuclear blood cells through microarray analysis. Mononuclear blood cells were isolated from four healthy non-smokers and plated in culture wells. Half of the cells were then exposed to 5 min of tobacco smoke. Fluorescent c-DNA probes were prepared from the linearly amplified m-RNAs for each sample and hybridized to cDNA microarrays representing approximately 30000 human genes. Significant increases or decreases in m-RNA gene expression between non-smoke-exposed and smoke-exposed samples were identified by permutation t-test, as implemented by the Significance Analysis of Microarrays software package. After smoke exposure, the expression of 90 genes with known function was significantly elevated and the expression of 19 genes with known function was significantly depressed. In addition, 18 upregulated and 26 downregulated transcripts were expressed sequence tags with little information available on function. Approximately 20 of the significantly elevated genes had previously been reported in the literature to be associated with periodontal pathogenesis (fold changes in parentheses). These included plasminogen activator (4.4), Heat Shock Protein (Hsp) 40 kD (2.2), thrombomodulin (4.2), cytochrome c (1.8), COX-2 (2.6), interleukin-1a (1.4), chemokine ligand 1 (3.8), cathepsin L (2.0), and calgranulin A (2.1). In addition, several significantly elevated genes not previously reported in the literature may also play a role in periodontal pathogenesis, and thus warrant further investigation. These include Diphtheria toxin receptor (heparin-binding epidermal growth factor-like growth factor) (7.8), Hsp 10 kDa (1.7), Hsp 105 kD (2.1), Hsp 70 kDa (1.6), and mitogen activated protein kinase 3 (1.5). Among the significantly depressed genes that may play a protective or destructive role in periodontal pathogenesis were interferon gamma receptor 2 (0.58) and chemokine receptor 2 (0.24). Our results may be of use in the search for the molecular mechanisms for the adverse effects of tobacco smoke on the host response.
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PMID:Alteration of gene expression profiles of peripheral mononuclear blood cells by tobacco smoke: implications for periodontal diseases. 1467 73

Deleted in bladder cancer 1 (DBC1) is a candidate gene for the bladder tumour suppressor locus at 9q33.1. The function of the gene is currently unknown but a cross-species sequence comparison suggests an important role, as it is highly evolutionarily conserved. Here, we transfected a nonexpressing human bladder cancer cell line with a set of human DBC1 cDNA constructs. The effect on global expression patterns was assessed using cDNA microarrays. The cell clone with the lowest level of DBC1 expression showed induced expression of 26 genes including plasminogen activator inhibitor 2 (SERPINB5; 4.6-fold), heparin-binding EGF-like growth factor precursor (DTR; 4.2-fold), small proline-rich protein 2B (SPRR2B; 3.6-fold), metallothionein 1 isoforms (MT1B/MT1A/MT-1F; from 2.9- to 3.2-fold), tissue-type plasminogen activator precursor (PLAT; 2.8-fold) and urokinase-type plasminogen activator precursor (PLAU; 2.7-fold). In clustering analysis, both PLAT and PLAU clustered with the functionally related urokinase plasminogen activator surface receptor (PLAUR; 1.9-fold). Furthermore, 14 human bladder tumours were analysed by real-time quantitative PCR using gene-specific primers for selected (n=20) genes. The expression levels of SERPINB5, PLAU, PLAUR and MT1 correlated with the DBC1 levels, suggesting previously unknown involvement of DBC1 in the urokinase-plasminogen pathway.
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PMID:DBC1 re-expression alters the expression of multiple components of the plasminogen pathway. 1636 96