Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intraalveolar fibrinolysis, is regulated by the concerted actions of plasmin, plasminogen activators (PAs), and their specific inhibitors (PAIs). This event is considered as a critical step in the pathogenesis of pulmonary fibrosis. The aim of this study was to evaluate whether local PA activity can be held as a marker of fibrosis in chronic interstitial lung disorders (ILD). Changes in both PA activity and PA-related proteins (urokinase-type PA (uPA), tissue-type PA (tPA), PAI-1 and PAI-2) were assessed in bronchoalveolar fluid (BALF) of 60 subjects: 18 healthy controls, 18 non-fibrotic sarcoidosis patients, 16 patients with idiopathic pulmonary fibrosis (IPF) and eight silicotic patients with established fibrosis. We observed a significant decrease of BALF PA activity in the three groups of patients as compared with controls. Reduction in BALF PA activity was compatible with lower uPA protein levels associated, especially in IPF patients, with an increased occurrence of PAI-1 and PAI-2 antigens. Soluble tPA antigen was never detected either in control subjects or in patients. Most importantly, the reduction in BALF PA activity and uPA protein levels was found to be most severe in patients with advanced fibrotic disease, namely IPF, while moderate and only weak alterations were found in silicosis and non-fibrotic sarcoidosis, respectively. In addition, significant positive correlations were found between BALF PA activity and functional impairment as assessed by TLC % and DLCO%. Finally, the reduction in uPA and PA activity levels observed in BALF from sarcoidosis patients was found to be proportional to the degree of BAL lymphocytosis. These findings indicate that an intense reduction in BALF PA activity is associated with severe stages of the parenchymal disease, possibly reflecting the degree of the fibrotic process.
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PMID:Depressed urokinase activity in bronchoalveolar lavage fluid from patients with sarcoidosis, silicosis or idiopathic pulmonary Rbrosis: relationship to disease severity. 2390 56

Silica is the major component of airborne dust generated by wind, manufacturing and/or demolition. Chronic occupational inhalation of silica dust containing crystalline quartz is by far the predominant form of silicosis in humans. Silicosis is a progressive lung disease that typically arises after a very long latency and is a major occupational concern with no known effective treatment. The mechanism of silicosis is not clearly understood. However, silicosis is associated with increased cell death, expression of redox enzymes and pro-fibrotic cytokines and chemokines. Since alveolar epithelial cell (AEC) death and disruption of alveolar fibrinolysis is often associated with both acute and chronic lung injuries, we explored whether p53-mediated changes in the urokinase-type plasminogen activator (uPA) system contributes to silica-induced lung injury. We further sought to determine whether caveolin-1 scaffolding domain peptide (CSP), which inhibits p53 expression, mitigates lung injury associated with exposure to silica. Lung tissues and AECs isolated from wild-type (WT) mice exposed to silica exhibit increased apoptosis, p53 and PAI-1, and suppression of uPA expression. Treatment of WT mice with CSP inhibits PAI-1, restores uPA expression and prevents AEC apoptosis by suppressing p53, which is otherwise induced in mice exposed to silica. The process involves CSP-mediated inhibition of serine-15 phosphorylation of p53 by inhibition of protein phosphatase 2A-C (PP2A-C) interaction with silica-induced caveolin-1 in AECs. These observations suggest that changes in the p53-uPA fibrinolytic system cross-talk contribute to lung injury caused by inhalation of silica dust containing crystalline quartz and is protected by CSP by targeting this pathway.
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PMID:Role of p53-fibrinolytic system cross-talk in the regulation of quartz-induced lung injury. 2559 29