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A multi-level model accounting for the effects of JAK2-STAT5 signal modulation in erythropoiesis

Paper ID Volume ID Publish Year Pages File Format Full-Text
15299 1401 2009 13 PDF Available
Title
A multi-level model accounting for the effects of JAK2-STAT5 signal modulation in erythropoiesis
Abstract

We develop a multi-level model, using ordinary differential equations, based on quantitative experimental data, accounting for murine erythropoiesis. At the sub-cellular level, the model includes a description of the regulation of red blood cell differentiation through Epo-stimulated JAK2-STAT5 signalling activation, while at the cell population level the model describes the dynamics of (STAT5-mediated) red blood cell differentiation from their progenitors. Furthermore, the model includes equations depicting the hypoxia-mediated regulation of hormone erythropoietin blood levels. Take all together, the model constitutes a multi-level, feedback loop-regulated biological system, involving processes in different organs and at different organisational levels.We use our model to investigate the effect of deregulation in the proteins involved in the JAK2-STAT5 signalling pathway in red blood cells. Our analysis results suggest that down-regulation in any of the three signalling system components affects the hematocrit level in an individual considerably. In addition, our analysis predicts that exogenous Epo injection (an already existing treatment for several blood diseases) may compensate the effects of single down-regulation of Epo hormone level, STAT5 or EpoR/JAK2 expression level, and that it may be insufficient to counterpart a combined down-regulation of all the elements in the JAK2-STAT5 signalling cascade.

Keywords
Systems biology; Signalling pathways; Cell population dynamics; Epo; Anaemia; Leukaemia; Hypoxia; Erythropoiesis
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A multi-level model accounting for the effects of JAK2-STAT5 signal modulation in erythropoiesis
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Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 33, Issue 4, August 2009, Pages 312–324
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us