| First Author | Yamamoto N | Year | 2015 |
| Journal | Mol Cell Endocrinol | Volume | 405 |
| Pages | 35-41 | PubMed ID | 25662279 |
| Mgi Jnum | J:221500 | Mgi Id | MGI:5640891 |
| Doi | 10.1016/j.mce.2015.02.002 | Citation | Yamamoto N, et al. (2015) Rac limits TGF-beta-induced VEGF synthesis in osteoblasts. Mol Cell Endocrinol 405:35-41 |
| abstractText | We previously showed that transforming growth factor-beta (TGF-beta) stimulates vascular endothelial growth factor (VEGF) synthesis via p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of Rac, which is a member of the Rho family of small GTPases, in the TGF-beta-stimulated VEGF synthesis in MC3T3-E1 cells. TGF-beta markedly increased the levels of GTP-bound Rac. NSC23766, a selective inhibitor of Rac-guanine nucleotide exchange factor interaction, significantly increased both the release of VEGF and the mRNA expression levels induced by TGF-beta. In addition, the release of VEGF stimulated by TGF-beta was amplified in Rac-knock down cells. Meanwhile, SIS3, a specific inhibitor of TGF-beta-dependent Smad3 phosphorylation, significantly reduced the TGF-beta-stimulated VEGF release. However, the phosphorylation of Smad2 or Smad3 induced by TGF-beta was hardly affected by NSC23766. On the other hand, NSC23766 enhanced the TGF-beta-induced phosphorylation of p38 MAP kinase without affecting the phosphorylation of p44/p42 MAP kinase or SAPK/JNK. Furthermore, the phosphorylation of p38 MAP kinase induced by TGF-beta was markedly upregulated in the Rac-knock down cells. These results strongly suggest that Rac negatively regulates the TGF-beta-stimulated VEGF synthesis via the inhibition of p38 MAP kinase in osteoblasts. |
