Insulin-like growth factor-I induces reactive oxygen species production and cell migration through Nox4 and Rac1 in vascular smooth muscle cells
| Autor: | Dan Meng, Jing（方靖） Fang, Dandan Lv |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
rac1 GTP-Binding Protein Time Factors Vascular smooth muscle Physiology medicine.medical_treatment Myocytes Smooth Muscle Muscle Smooth Vascular Rats Sprague-Dawley Cell Movement Physiology (medical) medicine Animals Myocyte RNA Messenger Insulin-Like Growth Factor I RNA Small Interfering Cells Cultured chemistry.chemical_classification Gene knockdown Reactive oxygen species NADPH oxidase biology urogenital system Growth factor NADPH Oxidases NOX4 Cell migration Rats Cell biology Matrix Metalloproteinase 9 Biochemistry chemistry NADPH Oxidase 4 cardiovascular system biology.protein Matrix Metalloproteinase 2 RNA Interference Reactive Oxygen Species Cardiology and Cardiovascular Medicine |
| Zdroj: | Cardiovascular Research. 80:299-308 |
| ISSN: | 0008-6363 |
| DOI: | 10.1093/cvr/cvn173 |
| Popis: | Aims We showed previously that insulin-like growth factor-I (IGF-I)-induced vascular smooth muscle cells (VSMCs) proliferation through the production of reactive oxygen species (ROS). However, how IGF-I-induced ROS was unknown. The aim of this study is to investigate the mechanisms by which IGF-I induces ROS production in VSMCs. Methods results Reverse transcription-PCR, real-time PCR, immunoblotting, and confocal microscopic image analysis were employed to determine protein expression, small Rho-GTPase Rac1 activation, and ROS production. Inhibition of NADPH oxidase 4 (Nox4) or Rac1 was performed by means of siRNA technology. Inhibition of Rac1 activity was accomplished using dominant-negative form of Rac1 (N17Rac1) plasmid. VSMCs from Sprague-Dawley rat thoracic aortas were used in this work.IGF-I enhanced ROS production in rat VSMCs. IGF-I increased the protein level of Nox4 but had little effect on its mRNA level. IGF-I induced the activation of Rac1. Either knockdown of Nox4 or inactivation of Rac1 impaired IGF-I-induced ROS. Over-expression of Nox4 increased NADPH oxidase activity, which was not influenced by inactivation of Rac1. Neither over-expression nor knockdown of Rac1 influenced Nox4 expression. Knockdown of Nox4 did not affect IGF-I-induced activation of Rac1. IGF-I increased matrix metalloproteinase (MMP)-2 and 9 activity and promoted VSMC migration, which was inhibited by knockdown of Nox4 and inactivation of Rac1. Conclusion Our results suggest that Nox4 and Rac1 mediate IGF-I-induced ROS production and cell migration in VSMCs and that Nox4 is not regulated by Rac1. |
| Databáze: | OpenAIRE |
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