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Mathematical modeling of the Phoenix Rising pathway.

Publication ,  Journal Article
Liu, C; Li, C-Y; Yuan, F
Published in: PLoS Comput Biol
February 2014

Apoptosis is a tightly controlled process in mammalian cells. It is important for embryogenesis, tissue homoeostasis, and cancer treatment. Apoptosis not only induces cell death, but also leads to the release of signals that promote rapid proliferation of surrounding cells through the Phoenix Rising (PR) pathway. To quantitatively understand the kinetics of interactions of different molecules in this pathway, we developed a mathematical model to simulate the effects of various changes in the PR pathway on the secretion of prostaglandin E2 (PGE2), a key factor for promoting cell proliferation. These changes include activation of caspase 3 (C3), caspase 7 (C7), and nuclear factor κB (NFκB). In addition, we simulated the effects of cyclooxygenase-2 (COX2) inhibition and C3 knockout on the level of secreted PGE2. The model predictions on PGE2 in MEF and 4T1 cells at 48 hours after 10-Gray radiation were quantitatively consistent with the experimental data in the literature. Compared to C7, the model predicted that C3 activation was more critical for PGE2 production. The model also predicted that PGE2 production could be significantly reduced when COX2 expression was blocked via either NFκB inactivation or treatment of cells with exogenous COX2 inhibitors, which led to a decrease in the rate of conversion from arachidonic acid to prostaglandin H2 in the PR pathway. In conclusion, the mathematical model developed in this study yielded new insights into the process of tissue regrowth stimulated by signals from apoptotic cells. In future studies, the model can be used for experimental data analysis and assisting development of novel strategies/drugs for improving cancer treatment or normal tissue regeneration.

Duke Scholars

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Published In

PLoS Comput Biol

DOI

EISSN

1553-7358

Publication Date

February 2014

Volume

10

Issue

2

Start / End Page

e1003461

Location

United States

Related Subject Headings

  • Signal Transduction
  • Prostaglandins E
  • Phospholipases A2
  • NF-kappa B
  • Models, Biological
  • Mice
  • Mathematical Concepts
  • Mammary Neoplasms, Experimental
  • Female
  • Cyclooxygenase 2 Inhibitors
 

Citation

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Liu, C., Li, C.-Y., & Yuan, F. (2014). Mathematical modeling of the Phoenix Rising pathway. PLoS Comput Biol, 10(2), e1003461. https://doi.org/10.1371/journal.pcbi.1003461
Liu, Chad, Chuan-Yuan Li, and Fan Yuan. “Mathematical modeling of the Phoenix Rising pathway.PLoS Comput Biol 10, no. 2 (February 2014): e1003461. https://doi.org/10.1371/journal.pcbi.1003461.
Liu C, Li C-Y, Yuan F. Mathematical modeling of the Phoenix Rising pathway. PLoS Comput Biol. 2014 Feb;10(2):e1003461.
Liu, Chad, et al. “Mathematical modeling of the Phoenix Rising pathway.PLoS Comput Biol, vol. 10, no. 2, Feb. 2014, p. e1003461. Pubmed, doi:10.1371/journal.pcbi.1003461.
Liu C, Li C-Y, Yuan F. Mathematical modeling of the Phoenix Rising pathway. PLoS Comput Biol. 2014 Feb;10(2):e1003461.

Published In

PLoS Comput Biol

DOI

EISSN

1553-7358

Publication Date

February 2014

Volume

10

Issue

2

Start / End Page

e1003461

Location

United States

Related Subject Headings

  • Signal Transduction
  • Prostaglandins E
  • Phospholipases A2
  • NF-kappa B
  • Models, Biological
  • Mice
  • Mathematical Concepts
  • Mammary Neoplasms, Experimental
  • Female
  • Cyclooxygenase 2 Inhibitors