Angiogenesis is essential for transplantation of mesenchymal stem cells (MSCs). Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors identified to date. Elevated VEGF levels in MSCs correlate with the potential of MSCs transplantation. As an indirect angiogenic agent, transforming growth factor-PI (TGF-beta 1) plays a pivotal role in the regulation of vasculogenesis and angiogenesis. However, the effect of TGF-beta 1 on VEGF synthesis in MSCs is still unknown. Besides, the intracellular signaling mechanism by which TGF-beta 1 stimulates this process remains poorly understood. In this article, we demonstrated that exposure of MSCs to TGF-beta 1 stimulated the synthesis of VEGF. Meanwhile, TGF-beta 1 stimulated the phosphorylation of Akt and extracellular signal-regulated kinase 1/2 (ERK1/2). Moreover, Ly 294002, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K)/Akt significantly attenuated the VEGF synthesis stimulated by TGF-beta 1. Additionally, U0126, a specific inhibitor of ERK1/2, also significantly attenuated the TGF-beta 1-stimulated VEGF synthesis. These results indicated that TGF-beta 1 enhanced VEGF synthesis in MSCs, and the Akt and ERK1/2 activation were involved in this process. (c) 2007 Elsevier Inc. All rights reserved.