A Central Role of PTP1B in Hyperinsulinemia-Enhanced IL-6 Signaling in Dedifferentiated Vascular Smooth Muscle CellsYingzi Chang*
Department of Pharmacology, A.T, Still University, Kirksville, MO 63501, USA
- *Corresponding Author:
- Yingzi Chang
Department of Pharmacology
A. T. Still University, Kirksville, MO 63501, USA
E-mail: [email protected]
Received date: January 20, 2011; Accepted date: March 02, 2011; Published date: March 04, 2011
Citation: Chang Y (2011) A Central Role of PTP1B in Hyperinsulinemia-Enhanced IL-6 Signaling in Dedifferentiated Vascular Smooth Muscle Cells. J Diabet Metabol 2:118. doi: 10.4172/2155-6156.1000118
Copyright: © 2011 Yingzi Chang. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Hyperinsulinemia is associated with an increased risk of vascular restenosis after angioplasty. As a major proinflammatory cytokine, interleukin-6 (IL-6) induces motogenic effects on vascular smooth muscle cells. Attenuation of vascular injury-induced neointima thickening was observed by blocking STAT3 tyrosine phosphorylation, which is a key component of IL-6 signaling. A non-receptor protein tyrosine phosphatase, PTP1B, plays a counter-regulatory role in injury-induced neointima formation by inhibiting platelet-derived growth factor (PDGF)-induced smooth muscle cell migration and proliferation. However, the role of IL-6, in association with hyperinsulinemia, with an increased risk of vascular restenosis and the involvement of PTP1B in this process has never been studied. Using subcultured (passages 5-9) smooth muscle cells isolated from rat aortae, we found that: 1) chronic insulin treatment potentiated IL-6-induced smooth muscle cell migration and STAT3 tyrosine phosphorylation; 2) chronic insulin dose-dependently suppressed the baseline expression of endogenous PTP1B; 3) overexpressing wild-type PTP1B significantly attenuated whereas C215S-PTP1B enhanced IL-6-induced STAT3 phosphorylation and smooth muscle cell migration. The aforementioned results suggest that inhibition of baseline expression of PTP1B and subsequent potentiation of IL-6-stimulated vascular smooth muscle migration may serve as a potential mechanism for increased risk of vascular restenosis after angioplasty in patients with insulin resistance.