Sitagliptin attenuates high glucose-induced alterations in migration, proliferation, calcification and apoptosis of vascular smooth muscle cells through ERK1/2 signal pathway

Lili Shi; Ye Ji; Dandan Liu; Ying Liu; Ying Xu; Yang Cao; Xiaoyan Jiang; Changqing Xu

doi:10.18632/oncotarget.20417

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Research Papers:

Sitagliptin attenuates high glucose-induced alterations in migration, proliferation, calcification and apoptosis of vascular smooth muscle cells through ERK1/2 signal pathway

Lili Shi, Ye Ji, Dandan Liu, Ying Liu, Ying Xu, Yang Cao, Xiaoyan Jiang _ and Changqing Xu

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Oncotarget. 2017; 8:77168-77180. https://doi.org/10.18632/oncotarget.20417

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Abstract

Lili Shi1,*, Ye Ji2,*, Dandan Liu1, Ying Liu1, Ying Xu1, Yang Cao1, Xiaoyan Jiang1 and Changqing Xu3

1Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China

2Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China

3Department of Pathophysiology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China

*These authors have contributed equally to this study

Correspondence to:

Xiaoyan Jiang, email: [email protected]

Changqing Xu, email: [email protected]

Keywords: vascular smooth muscle cells, atherosclerosis, diabetes, high glucose, dipeptidyl peptidase-4 inhibitor

Received: March 02, 2017 Accepted: June 05, 2017 Published: August 24, 2017

ABSTRACT

Background/Aims: This study investigated the effects of sitagliptin on migration, proliferation, calcification and apoptosis of vascular smooth muscle cells (VSMCs) under high glucose (HG) conditions.

Methods: VSMCs were isolated from the thoracic aorta of Sprague Dawley rats. The cultured VSMCs were subjected to control medium, mannitol medium, HG medium (25 mM), pretreatment with 200 nM sitagliptin in control or HG medium, or the ERK1/2 inhibitor PD98059 in HG medium. Cell proliferation, migration, apoptosis and calcification were determined.

Results: HG conditions promoted the proliferation, migration, calcification and impairment of apoptosis in VSMCs compared with controls (P<0.05). Pretreatment with sitagliptin effectively attenuated proliferation, migration, calcification of cells and increased apoptosis of HG-cultured VSMCs as compared with the HG group (P<0.05). Culture with HG resulted in the up-regulation of p-ERK1/2 in VSMCs, whereas sitagliptin pretreatment could inhibit HG-induced p-ERK1/2 expression. In addition, the ERK1/2 inhibitor PD98059, inhibited proliferation, migration, calcification and promoted the apoptosis of HG-cultured VSMCs compared with the HG group (P<0.05).

Conclusion: The effects of sitagliptin on VSMC under high glucose condition were achieved through ERK1/2 signaling pathways.

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Research Papers:

Sitagliptin attenuates high glucose-induced alterations in migration, proliferation, calcification and apoptosis of vascular smooth muscle cells through ERK1/2 signal pathway

Abstract