High glucose promotes vascular smooth muscle cell proliferation by upregulating proto-oncogene serine/threonine-protein kinase Pim-1 expression.

High glucose promotes vascular smooth muscle cell proliferation by upregulating proto-oncogene serine/threonine-protein kinase Pim-1 expression.
Oncotarget. 2017 Oct 24;8(51):88320-88331
Authors: Wang K, Deng X, Shen Z, Jia Y, Ding R, Li R, Liao X, Wang S, Ha Y, Kong Y, Wu Y, Guo J, Jie W
Abstract
Serine/threonine kinase proviral integration site for Moloney murine leukemia virus 1 (Pim-1) plays an essential role in arterial wall cell proliferation and associated vascular diseases, including pulmonary arterial hypertension and aortic wall neointima formation. Here we tested a role of Pim-1 in high-glucose (HG)-mediated vascular smooth muscle cell (VSMC) proliferation. Pim-1 and proliferating cell nuclear antigen (PCNA) expression levels in arterial samples from streptozotocin-induced hyperglycemia rats were increased, compared with their weak expression in normoglycemic groups. In cultured rat VSMCs, HG led to transient Pim-1 expression decline, followed by sustained expression increase at both transcriptional and translational levels. Immunoblot analysis demonstrated that HG increased the expression of the 33-kDa isoform of Pim-1, but at much less extent to its 44-kDa plasma membrane isoform. D-glucose at a concentration of 25 mmol/L showed highest activity in stimulating Pim-1 expression. Both Pim-1 inhibitor quercetagetin and STAT3 inhibitor stattic significantly attenuated HG-induced VSMC proliferation and arrested cell cycle pro...

Source: Oncotarget - November 29, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research