期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 316, 期 2, 页码 C186-C197出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00428.2018
关键词
diabetes mellitus; endothelial cells; phenotypic switching; platelet adhesion; vascular smooth muscle cells
资金
- National Natural Science Foundation of China [81800434, 81570263]
- Foundation of Luzhou Municipal Science and Technology Bureau Grants [2017LZXNYD-T05, 2016LZX-NYD-J24]
- American Heart Association Scientist Development Grant [10SDG2570037]
Platelet (PLT)-endothelial cell (EC) interaction appears to contribute to phenotypic transition of vascular smooth muscle cells (VSMCs), which play an important role in the physiological and pathological process of vascular complications in type 2 diabetes mellitus (DM2). However, the precise mechanisms by which interactions between PLTs and ECs affect VSMC phenotype have largely remained unclear. We determined the effect of diabetic PLT-EC interaction to influence VSMC migration, proliferation, and phenotypic transformation in triple-cell coculture models using the quantitative real-time PCR, Western blot, fluorescence microscopy, wound scratch assays, CCK-8 assays. and gelatin zymography assays. Our results revealed DM2 PLT-EC interaction to be associated with a significant down-regulation of VSMC-specific contractile phenotypic genes and proteins, including SM22 alpha, smooth muscle actin, Smoothelin-B, and smooth muscle-myosin heavy chain. Inversely, VSMC-specific proliferative phenotype gene and protein levels, including cyclin D1 and 2, nontnuscle myosin heavy chain B, and PCNA were in upregulation. Furthermore, the DM2-originated pur-Ec interaction promoted the expression level of transforming growth factor-beta 1, and the PI3K/Akt and matrix metalloproteinase 9 signaling pathway was activated subsequently. Finally, these reactions contributed to a synthetic phenotype of VSMCs, including the proliferation, migration, and gelatinolytic activities. These findings suggest that PLT-EC interaction modulates the phenotypic transition of VSMCs between a contractile and proliferative/synthetic phenotype under diabetic conditions, conceivably providing important implications regarding the mechanisms controlling the VSMC phenotypic transition and the development of cardiovascular complications.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据