Alveolar epithelial cell plasminogen activator. Characterization and regulation
B C Marshall1, D S Sageser, N V Rao
1Department of Human Genetics, University of Utah Medical Center, Salt Lake City 84132.
The Journal of Biological Chemistry
|May 15, 1990
Summary
Rat alveolar epithelial cells synthesize urokinase-type plasminogen activator (u-PA), crucial for fibrinolysis in acute lung injury repair. This finding highlights their role in lung tissue remodeling.
Area of Science:
- Cell Biology
- Pulmonary Medicine
- Biochemistry
Background:
- Intra-alveolar fibrin deposition is a key pathological feature of acute lung injury (ALI).
- Alveolar epithelial cells are critical for lung repair processes following ALI.
Purpose of the Study:
- To investigate the potential of alveolar epithelial cells to produce plasminogen activators (PAs).
- To characterize the type and regulation of PA produced by these cells.
Main Methods:
- Primary rat alveolar epithelial cells were cultured.
- Plasminogen activator activity and mRNA levels were measured.
- Effects of phorbol myristate acetate (PMA), dexamethasone, and cycloheximide on u-PA production were assessed.
Main Results:
- Alveolar epithelial cells synthesize and secrete a PA with urokinase-type (u-PA) properties.
- PMA upregulates u-PA synthesis, likely via protein kinase C.
- Dexamethasone partially inhibits PMA-induced u-PA activity, while cycloheximide completely inhibits it.
- PMA induces u-PA gene expression and mRNA accumulation, independent of intermediate protein synthesis.
Conclusions:
- Alveolar epithelial cells produce u-PA, contributing to fibrinolysis.
- Epithelial cell-derived u-PA plays a significant role in the lung tissue remodeling following acute lung injury.
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