Insulin-like growth factor-I (IGF-I) plays an important role in proliferation of vascular smooth muscle cells (VSMCs). However, the mechanism that IGF-I induces VSMCs proliferation is not completely understood. In this study, we determined (a) whether and how IGF-I induces transactivation of epidermal growth factor receptor (EGFR) in primary rat aortic VSMCs, (b) the contribution of EGFR to IGF-I-stimulated activation of extracellular signal-regulated kinase (ERK) and cell proliferation, and (c) the role of reactive oxygen species (ROS) in the cellular function. We showed that IGF-I induced phosphorylation of EGFR and ERK1/2 in VSMCs. AG1478, an EGFR inhibitor, inhibited IGF-I-induced phoshorylation of EGFR and ERK1/2. IGF-I stimulated ROS production and Src activation. Antioxidants inhibited IGF-I-induced ROS generation and activation of EGFR, ERK, and Src. Src kinase inhibitor PP1 and Src siRNA blocked IGF-I-induced activation of EGFR and ERK1/2. Inhibition of IGF-I-stimulated EGFR activation inhibited IGF-I-induced VSMC proliferation. These results suggest that (1) IGF-I induces EGFR activation through production of ROS and ROS-mediated Src activation in VSMCs, and (2) EGFR transactivation is required for IGF-I-induced VSMC proliferation.
|Number of pages||10|
|Journal||Free Radical Biology and Medicine|
|State||Published - Jun 1 2007|
Bibliographical noteFunding Information:
This study was supported by grants from the National Natural Science Foundation of China (NO.30470361 and 30570962) and grants from Shanghai Municipal Commission of Science and Technology (05DJ14009, 04DZ14007), and by a grant from the National Cancer Institute, NIH (CA109460). Dan Meng is supported by grants from the National Natural Science Foundation of China (NO.30600245) and Postdoctoral Science Foundation of China. We thank Bei-Bei Fu for her assistance in the cell culture.
- Epidermal growth factor receptor
- Insulin-like growth factor-I
- Reactive oxygen species
- Vascular smooth muscle cell
ASJC Scopus subject areas
- Physiology (medical)