西他列汀通过ERK1/2信号通路减轻高糖诱导的血管平滑肌细胞迁移、增殖、钙化和凋亡的改变。

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

作者信息

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

机构信息

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

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

出版信息

Oncotarget. 2017 Aug 24;8(44):77168-77180. doi: 10.18632/oncotarget.20417. eCollection 2017 Sep 29.

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.

背景/目的：本研究调查了西他列汀在高糖（HG）条件下对血管平滑肌细胞（VSMC）迁移、增殖、钙化和凋亡的影响。

方法

从Sprague Dawley大鼠胸主动脉分离VSMC。将培养的VSMC置于对照培养基、甘露醇培养基、HG培养基（25 mM）、在对照或HG培养基中用200 nM西他列汀预处理，或在HG培养基中用ERK1/2抑制剂PD98059处理。测定细胞增殖、迁移、凋亡和钙化情况。

结果

与对照组相比，HG条件促进了VSMC的增殖、迁移、钙化并损害了其凋亡（P<0.05）。与HG组相比，用西他列汀预处理可有效减弱细胞的增殖、迁移、钙化，并增加HG培养的VSMC的凋亡（P<0.05）。HG培养导致VSMC中p-ERK1/2上调，而西他列汀预处理可抑制HG诱导的p-ERK1/2表达。此外，与HG组相比，ERK1/2抑制剂PD98059抑制了HG培养的VSMC的增殖、迁移、钙化并促进了其凋亡（P<0.05）。