The Effects of RBP4 and Vitamin D on the Proliferation and Migration of Vascular Smooth Muscle Cells via the JAK2/STAT3 Signaling Pathway

Abstract

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are one of the main causes of the development of diabetic atherosclerotic process. The aim of our study was to assess the role of RBP4 in the proliferation and migration of VSMCs and the inhibitory effect of vitamin D on the mechanisms. In an in vivo experiment, rats were randomly classified into 6 groups: the control group, diabetic rats, diabetic atherosclerotic rats (diabetic rats intraperitoneally injected with RBP4), diabetic atherosclerotic rats treated with 0.075 μg kg-1 d-1 vitamin D, 0.15 μg kg-1 d-1 vitamin D and 0.3 μg kg-1 d-1 vitamin D. We found that the levels of JAK2, STAT3, cylinD1, and Bcl-2 were increased in diabetic atherosclerotic rats, and these increases were improved after vitamin D supplementation. Furthermore, to investigate the underlying molecular mechanisms, cells were cultured with glucose in the presence of RBP4 and the absence of RBP4, respectively, and vitamin D of different concentrations and different intervention times was simultaneously adopted. The proliferation and migration of VSMCs was enhanced and the levels of JAK2, STAT3, cyclinD1, and Bcl-2 were increased in the cells transfected with RBP4 overexpression plasmid. Moreover, vitamin D supplementation was detected to lower the expressions of JAK2, STAT3, cyclinD1, and Bcl-2 and inhibit the abnormal proliferation of VSMCs caused by the RBP4/JAK2/STAT3 signaling pathway. RBP4 can promote the proliferation and migration of VSMCs and contributes to the development of diabetic macroangiopathy via regulating the JAK2/STAT3 signaling pathway. This mechanism of RBP4 can be inhibited by vitamin D supplementation.