Network Modeling Approach to Predict Myofibroblast Differentiation.
Network Modeling Approach to Predict Myofibroblast Differentiation.
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网络建模方法预测肌纤维细胞分化。
DOI：
10.1007/s12195-014-0344-9
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发表时间：
2014-09
影响因子：
2.8
通讯作者：
Merryman WD
中科院分区：
文献类型：
--
作者：
Schroer AK;Ryzhova LM;Merryman WD
Fibrotic disease is a major cause of morbidity and mortality and is characterized by the transition of resident fibroblast cells into active myofibroblasts, identified by their expression of alpha smooth muscle actin. Myofibroblast differentiation is regulated by growth factor signaling and mechanical signals transduced through integrins, which converge at focal adhesion proteins (Src and FAK) and MAPK signaling, but lead to divergent outcomes. While details are known about individual pathways, little is known about their interactions. To this end, an ODE-based model of this cell signaling network was developed in parallel with in vitro experiments to analyze potential mechanisms of crosstalk and regulation of αSMA production. We found that cells lacking Src or FAK produce significantly less or more αSMA than wild type cells, respectively. Transforming growth factor beta 1 and fibroblast growth factor signal through ERK and MAPK p38 with different dynamic profiles to increase or decrease αSMA expression, respectively. Our model effectively recreated αSMA expression levels across a set of 22 experimental conditions and matched some features of transient phosphorylation of ERK and p38. These results support a potential mechanism for regulation of fibroblast differentiation: αSMA production is promoted by active p38 and Src and opposed by ERK.
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DOI：
10.1083/jcb.147.2.401
发表时间：
1999-10-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ivaska J;Reunanen H;Westermarck J;Koivisto L;Kähäri VM;Heino J
通讯作者：
Heino J
影响因子：
9.3
作者：
Caraci, Filippo;Gili, Elisa;Vancheri, Carlo
通讯作者：
Vancheri, Carlo
DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert PM;Havenstrite KL;Magnusson KE;Sacco A;Leonardi NA;Kraft P;Nguyen NK;Thrun S;Lutolf MP;Blau HM
通讯作者：
Blau HM
影响因子：
3.7
作者：
Hsu HJ;Lee CF;Locke A;Vanderzyl SQ;Kaunas R
通讯作者：
Kaunas R
DOI：
10.1161/01.atv.0000136548.17816.07
发表时间：
2004-08-01
影响因子：
8.7
作者：
Kawai-Kowase, K;Sato, H;Kurabayashi, M
通讯作者：
Kurabayashi, M