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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Prostaglandin E(2) induces fibroblast apoptosis by modulating multiple survival pathways
Steven K Huang1, Eric S White, Scott H Wettlaufer
1Pulmonary and Critical Care Medicine, University of Michigan, 6301 MSRB III, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-5642, USA.
Summary
Prostaglandin E2 (PGE2) surprisingly induces apoptosis in normal lung fibroblasts, contrasting its known antifibrotic roles. Fibrotic lung cells, however, show resistance to this cell death pathway.
Area of Science:
- Cell Biology
- Molecular Medicine
- Pulmonary Research
Background:
- Prostaglandin E2 (PGE2), a lipid mediator, is known to inhibit fibroblast functions, suggesting antifibrotic properties.
- The role of PGE2 in regulating fibroblast survival and apoptosis, particularly in the context of lung fibrosis, remains largely unexplored.
Purpose of the Study:
- To investigate the effects of PGE2 on apoptosis and associated signaling pathways in normal and fibrotic lung fibroblasts.
- To elucidate the molecular mechanisms underlying PGE2-induced apoptosis in lung fibroblasts.
Main Methods:
- Treatment of normal and fibrotic lung fibroblasts with varying concentrations of PGE2.
- Assessment of apoptosis using Annexin V staining, caspase activity assays, and detection of cleaved poly-ADP-ribose polymerase (PARP).
- Analysis of signaling pathways involving EP2/EP4 receptors, caspases 8 and 9, PTEN, Akt, survivin, and Fas expression.
Main Results:
- PGE2 significantly increased apoptosis in normal lung fibroblasts in a dose-dependent manner.
- PGE2-induced apoptosis involved EP2/EP4 receptor signaling, activation of caspases 8 and 9, decreased Akt activity, and altered expression of survivin and Fas.
- Fibroblasts from patients with pulmonary fibrosis demonstrated resistance to the pro-apoptotic effects of PGE2.
Conclusions:
- Contrary to its effects on other cell types, PGE2 promotes apoptosis in lung fibroblasts via multiple signaling pathways.
- These findings reveal a novel mechanism by which PGE2 may inhibit or reverse fibrogenesis in interstitial lung diseases.
- The resistance of fibrotic lung fibroblasts to PGE2-induced apoptosis highlights a potential therapeutic target for lung fibrosis.
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