Insulin-like growth factor-1 increases endothelin receptor A levels and action in cultured rat aortic smooth muscle cells

✍ Scribed by Ching Fai Kwok; Chi-Chang Juan; Kuang-Chung Shih; Chii-Min Hwu; Tjin-Shing Jap; Low-Tone Ho

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 176 KB
• Volume: 94
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20321

✦ Synopsis

Abstract

Insulin is known to cause an increase in endothelin‐1 (ET‐1) receptors in vascular smooth muscle cells (SMCs), but the effect of insulin‐like growth factor 1 (IGF‐1) on ET‐1 receptor expression is not known. We therefore carried out the present study to determine the effect of IGF‐1 on the binding of ET‐1 to, and ET type A receptor (ETAR) expression and ET‐1‐induced ^3^H‐thymidine incorporation in, vascular SMCs. In serum‐free medium, IGF‐1 treatment increased the binding of ^125^I‐ET‐1 to SMC cell surface ET receptors from a specific binding of 20.1% ± 3.1% per mg of protein in control cells to 45.1% ± 8.6% per mg of protein in cells treated with IGF‐1 (10 nM). The effect of IGF‐1 was dose‐related, with a significant effect (1.4‐fold) being seen at 1 nM. The minimal time for IGF‐1 treatment to be effective was 30 min and the maximal effect was reached at 6 h. Immunoblotting analysis showed that ETAR expression in IGF‐1‐treated cells was increased by 1.7‐fold compared to controls. Levels of ETAR mRNA measured by the RT‐PCR method and Northern blotting were also increased by 2‐fold in IGF‐1‐treated SMCs. These effects of IGF‐1 were abolished by cycloheximide or genistein. Finally, ET‐1‐stimulated thymidine uptake and cell proliferation were enhanced by IGF‐1 treatment, with a maximal increase of 3.2‐fold compared to controls. In conclusion, in vascular SMCs, IGF‐1 increases the expression of the ET‐1 receptor in a dose‐ and time‐related manner. This effect is associated with increased thymidine uptake and involves tyrosine kinase activation and new protein synthesis. These findings support the role of IGF‐1 in the development of atherosclerotic, hypertensive, and diabetic vascular complications. © 2004 Wiley‐Liss, Inc.