Tissue Factor Signals Airway Epithelial Basal Cell Survival via Coagulation and PAR1/2.
ABSTRACT Rationale: Tissue factor (TF) initiates the extrinsic coagulation cascade and is a high affinity receptor for coagulation factor VII. TF also participates in Protease Activated Receptor, PAR1 and PAR2, activation. Human epithelial basal cells were previously purified on the basis of tissue factor (TF) expression. Objective: The purpose of this study was to determine if tracheobronchial epithelial basal cell-associated TF drives coagulation and/or activates PARs to promote basal cell functions. Methods: We utilized human tracheobronchial tissues to isolate human airway epithelial cells using specific cell surface markers by flow cytometry and studied TF expression by immunostaining. TF-dependent fibrin network formation was observed by confocal and scanning electron microscopy (SEM). TF knockdown was done using shRNA, and TF mRNA was measured using quantitative RT-PCR. Results: We found that 97±5% of first passage human tracheobronchial epithelial cells were basal cells, and 100% of these basal cells expressed TF. Basal cell-associated TF was active, but TF activity was dependent on added extrinsic coagulation cascade factors. TF inhibition caused basal cell apoptosis and necrosis. This was due to two parallel but interdependent TF-regulated processes: failure to generate a basal cell-associated fibrin network and suboptimal PAR1/2 activity. Conclusions: The data indicates that membrane surface TF mediates airway epithelial basal cell attachment, which maintains cell survival and mitotic potential. The implications of these findings are discussed in the context of basal cell-associated TF activity in normal and injured tissues, and potential for repair of airway epithelium in lung disease.
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- "The new amino terminus functions as a tethered ligand and activates the receptor . Recent reports suggest that PAR2 is involved in the regulation of apoptosis . Since defective of apoptosis plays a crucial role in the pathogenesis of cancer, we hypothesized that PAR2 might be involved in the regulation of glioma cell apoptosis. "
ABSTRACT: The pathogenesis of glioma is unclear. The disturbance of the apoptosis process plays a critical role in glioma growth. Factors regulating the apoptosis process are to be further understood. This study aims to investigate the role of protease activated receptor-2 (PAR2) in regulation the apoptosis process in glioma cells. The results showed that U87 cells and human glioma tissue expressed PAR2. Exposure to tryptase, or the PAR2 active peptide, increased STAT3 phosphorylation in the radiated U87 cells, reduced U87 cell apoptosis, suppressed the expression of p53 in U87 cells. Activation of PAR2 can reduce the radiated U87 cell apoptosis via modulating the expression of p53. The results implicate that PAR2 may be a novel therapeutic target in the treatment of glioma.Journal of Biomedical Science 03/2014; 21(1):25. DOI:10.1186/1423-0127-21-25 · 2.76 Impact Factor
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ABSTRACT: A conference, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases", was held July 25-28, 2011 at the University of Vermont, to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy and ex vivo bioengineering approaches for lung diseases. These are rapidly expanding areas of study that both provide further insight into and challenge traditional views of mechanisms of lung repair after injury and pathogenesis of several lung diseases. The goals of the conference were to summarize the current state of the field, discuss and debate current controversies, and to identify future research directions and opportunities for both basic and translational research in cell based therapies for lung diseases. The goal of this article, which accompanies the formal conference report, is to provide a comprehensive review of the published literature in lung regenerative medicine from the last conference report through December 2012.Annals of the American Thoracic Society 07/2013; 10(5). DOI:10.1513/AnnalsATS.201304-090AW