Prostaglandin E1 Inhibited Diabetes-Induced Phenotypic Switching of Vascular Smooth Muscle Cells Through Activating Autophagy

Cellular Physiology and Biochemistry

Xing-Rong An¹ 

关键词: Diabetes;    Phenotype switching;    Autophagy;    AKT;    MTOR;    PGE1;   

DOI  :  10.1159/000494240

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims The phenotype switching of vascular smooth muscle cells (VSMCs) was associated with the onset or progression of the atherogenic process in type 2 diabetes mellitus (T2DM). Alprostadil (Prostaglandin E1, PGE1) as a bioactive drug had a protective effect on vascular function. However, it is unknown whether PGE1 inhibited the phenotype switching in VSMCs via autophagy, which played a protective role in the vascular complications of diabetes. Methods The phenotype switching was induced by high glucose (HG, 25mM) in VSMCs, the protein expression was measured by western blot analysis and immunofluorescent staining. In vivo study, vascular lesion and dysfunction were produced in the rats fed with high fat diet (HFD) combined with low dose streptozotocin (STZ) administration. Results The decrease of α-SMA and the increase of vimentin, collagen I and proliferating cell nuclear antigen (PCNA) were found in HG-treated VSMCs. Along with more abundance of p62, autophagy markers LC3B and Beclin-1 significantly decreased in VSMCs exposed to HG. Such abnormal changes were significantly reversed by PGE1, which mimicked the role of autophagy activator rapamycin and was dramatically counteracted by 3-methyladenine, an autophagy inhibitor. Furthermore, PGE1 suppressed the phosphorylation of AKT and mTOR, which negatively regulated autophagy level in VSMCs. In vivo study, PGE1 remarkably improved the endothelium-independent contraction of thoracic aorta and restored the expression of α-SMA, osteopontin, LC3B, phosphorylated mTOR in the artery media of T2DM rats. Conclusion These results demonstrated that PGE1 maintained the phenotype of VSMCs via the AKT/mTOR-dependent autophagy, which prevented diabetes-induced vascular complications.

【 授权许可】

CC BY-NC-ND