Thromboxane A₂modulates migration, proliferation, and differentiation of adipose tissue-derived mesenchymal stem cells

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 A 2 (TxA 2 ) mimetic U46619 strongly stimulated migration and proliferation of human adipose tissue-derived MSCs (hADSCs). Furthermore, U46619 treatment increased expression of α-smooth muscle actin (α-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 α-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.

Thromboxane Governs the Differentiation of Adipose-Derived Stromal Cells Toward Endothelial Cells In Vitro and In Vivo

“…However, others reported that TP blockers suppressed migration and angiogenesis of human umbilical vein ECs and human dermal microvascular ECs, 44 TxAS overexpression observed in nonsmall cell lung cancers promotes tumor growth and VEGF secretion, 45,46 and activation of TP induced the differentiation of human ASCs to smooth muscle-like cells. 47,48 The discrepancies are probably ascribed to different cells and different approaches used, and perhaps different downstream signaling is mediated by TP receptors.…”

Inhibition of FAAH confers increased stem cell migration via PPARα

“…Moreover, activation of p42/44 MAPK, an essential intracellular trigger of migratory behavior of stem cells ( 45,46 ), has recently been shown to confer the promigratory effect of cannabidiol on MSCs ( 33 ). However, the impact of the endocannabinoids, AEA and 2-AG, or the endocannabinoid-like substances, OEA and PEA, on the migratory action of MSCs is largely unknown.…”

Essential fatty acids and their metabolites as modulators of stem cell biology with reference to inflammation, cancer, and metastasis

“…Thromboxane A 2 , a product of AA metabolism, appears to play a key role in the migration, proliferation, and differentiation of human adipose tissuederived mesenchymal stem cells into smooth muscle-like cells through signaling mechanisms involving ERK and p38 MAPK [89]. This action of TXA 2 on migration and proliferation of stem cells may have relevance to the metastatic properties shown by some tumor cells.…”