Exp Mol Med.  2009 Jan;41(1):17-24. 10.3858/emm.2009.41.1.003.

Thromboxane A2 modulates migration, proliferation, and differentiation of adipose tissue-derived mesenchymal stem cells

• Yun DH
• Song HY
• Lee MJ
• Kim MR
• Kim MY
• Lee JS
• Kim JH

• KMID: 756282
• DOI: http://doi.org/10.3858/emm.2009.41.1.003

Abstract

Prostanoid metabolites are key mediators in inflammatory responses, and accumulating evidence suggests that mesenchymal stem cells (MSCs) can be recruited to injured or inflamed tissues. In the present study, we investigated whether prostanoid metabolites can regulate migration, proliferation, and differentiation potentials of MSCs. We demonstrated herein that the stable thromboxane A2 (TxA2) mimetic U46619 strongly stimulated migration and proliferation of human adipose tissue-derived MSCs (hADSCs). Furthermore, U46619 treatment increased expression of alpha-smooth muscle actin (alpha-SMA), a smooth muscle marker, in hADSCs, suggesting differentiation of hADSCs into smooth muscle-like cells. U46619 activated ERK and p38 MAPK, and pretreatment of the cells with the MEK inhibitor U0126 or the p38 MAPK inhibitor SB202190 abrogated the U46619-induced migration, proliferation, and alpha-SMA expression. These results suggest that TxA2 plays a key role in the migration, proliferation, and differentiation of hADSCs into smooth muscle-like cells through signaling mechanisms involving ERK and p38 MAPK.

Keyword

cell movement; cell proliferation; 15-hydroxy-11alpha, 9alpha-(epoxymethano)prosta-5, 13-dienoic acid; mesenchymal stem cells; mitogen-activated protein kinase 1; mitogen-activated protein kinase 14; thromboxane A2

MeSH Terms

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology
Adipose Tissue/*cytology
*Cell Physiological Processes/drug effects
Cells, Cultured
Extracellular Signal-Regulated MAP Kinases/metabolism
Humans
Mesenchymal Stem Cells/*cytology
Receptors, Thromboxane A2, Prostaglandin H2/metabolism
Signal Transduction
Thromboxane A2/*metabolism
p38 Mitogen-Activated Protein Kinases/metabolism