Abstract
Although it is known that transforming growth factor (TGF)‐β induces vascular endothelial growth factor (VEGF) synthesis in vascular smooth muscle cells, the underlying mechanisms are still poorly understood. In the present study, we examined whether the mitogen‐activated protein (MAP) kinase superfamily is involved in TGF‐β‐stimulated VEGF synthesis in aortic smooth muscle A10 cells. TGF‐β stimulated the phosphorylation of p42/p44 MAP kinase and p38 MAP kinase, but not that of SAPK (stress‐activated protein kinase)/JNK (c‐Jun N‐terminal kinase). The VEGF synthesis induced by TGF‐β was not affected by PD98059 or U0126, specific inhibitors of the upstream kinase that activates p42/p44 MAP kinase. We confirmed that PD98059 or U0126 did actually suppress the phosphorylation of p42/p44 MAP kinase by TGF‐β in our preparations. PD169316 and SB203580, specific inhibitors of p38 MAP kinase, significantly reduced the TGF‐β‐stimulated synthesis of VEGF (each in a dose‐dependent manner). PD169316 or SB203580 attenuated the TGF‐β‐induced phosphorylation of p38 MAP kinase. These results strongly suggest that p38 MAP kinase plays a part in the pathway by which TGF‐β stimulates the synthesis of VEGF in aortic smooth muscle cells. J. Cell. Biochem. 82: 591–598, 2001. © 2001 Wiley‐Liss, Inc.