Korean J Physiol Pharmacol.  2007 Feb;11(1):31-36.

The Role of Janus Kinase in Superoxide-mediated Proliferation of Diabetic Vascular Smooth Muscle Cells

• Lee JY
• Park JY
• Kim CD

Abstract

To elucidate a potential molecular link between diabetes and atherosclerosis, we investigated the role of Janus tyrosine kinase (JAK) for NAD(P)H oxidase-derived superoxide generation in the enhanced proliferative capacity of vascular smooth muscle cells (VSMC) of Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of type 2 diabetes. An enhanced proliferative response to 10% fetal bovine serum (FBS) and superoxide generation with an increased NAD(P)H oxidase activity were observed in diabetic (OLETF) VSMC. Both the enhanced proliferation and superoxide generation in diabetic VSMC were significantly attenuated by AG490, JAK2 inhibitor, and PP2, Src kinase inhibitor. Tyrosine phosphorylation of proteins in diabetic VSMC, especially JAK2, was increased compared to control VSMC. Furthermore, the enhanced NAD(P)H oxidase activity in diabetic VSMC was significantly attenuated by AG490 in a dose-dependent manner. Together, these results indicate that the signal pathway which leads to diabetes-associated activation of Src kinase/JAK is critically involved in the diabetic VSMC proliferation through NAD(P)H oxidase activation and superoxide generation.

Keyword

JAK2; VSMC; Superoxide; Proliferation; NAD(P)H oxidase

MeSH Terms

Animals
Atherosclerosis
Models, Animal
Muscle, Smooth, Vascular*
NADPH Oxidase
Phosphorylation
Phosphotransferases*
Protein-Tyrosine Kinases
Rats
Signal Transduction
Superoxides
Tyrosine
NADPH Oxidase
Phosphotransferases
Protein-Tyrosine Kinases
Superoxides
Tyrosine