|
- 2018
miR-132在人脐静脉内皮细胞中的生物学功能
|
Abstract:
摘要 目的: 探讨动脉粥样硬化组织中miRNA-132的表达及其对内皮细胞增殖、凋亡及脂代谢的影响.方法:用Real-time PCR法检测48例动脉粥样硬化患者组织与正常动脉组织的表达量;培养人脐静脉内皮细胞,分别转染miR-132 inhibitor及阴性对照,检测细胞的增殖、凋亡;利用Western blot检测相关基因表达变化.结果:抑制miR-132 表达,内皮细胞的增殖增强,凋亡减少;增殖相关基因PCNA和KLF5升高及凋亡相关基因表达降低.结论:miR-132抑制HUVEC细胞的增殖,并在体外诱导细胞凋亡,miR-132可能抑制动脉粥样硬化的形成,其抑制功能可能通过下游PCNA和KFLs而实现.
[1] | SCHOBER A, SCHOBER A, NAZARIJAHANTIGH M, et al. MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1[J]. Nature Medicine, 2014, 20(4): 368-376. |
[2] | LI J J, HAN M, WEN J K, et al. Osteopontin stimulates vascular smooth muscle cell migration by inducing FAK phosphorylation and ILK dephosphorylation[J]. Biochemical & Biophysical Research Communications, 2007, 356(1): 13. |
[3] | CERSOSIMO E, DEFRONZO R A. Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases[J].Diabetes Metab Res Rev,2006,22(6):423-436. |
[4] | ZHANG X H, ZHENG B, HAN M, et al. Synthetic retinoid Am80 inhibits interaction of KLF5 with RARα through inducing KLF5 dephosphorylation mediated by the PI3K/Akt signaling in vascular smooth muscle cells[J]. Febs Letters, 2009, 583(8): 1231-1236. |
[5] | GAO D, NIU X, NING N, et al. Regulation of angiotensin II-induced Krüppel-like factor 5 expression in vascular smooth muscle cells[J]. Biological & Pharmaceutical Bulletin, 2006, 29(10): 2004-2008. |
[6] | LEINNOEN M, SOIKLSU P. Infection and atherosclerosis[J].Scand Cardiovasc J, 2002, 34(2):12-20. |
[7] | OONI K, ALA-KORPEL M. Modified LDL-trigger of atherosclerosis and inflammation in the arterial intima[J]. J Inter Med, 2000,247:359-370. |
[8] | 黄显莹,符方勇,陈清,等. miR-132诱导动脉粥样硬化中血管内皮细胞的促炎性作用.miR-132 induces the pro-inflammatory of vascular endothelial cells in atherosclerosis [J]. 实用医学杂志,2016,32(5):20-22. |
[9] | MOORE K, TABAS I. Macrophages in the Pathogenesis of atherosclerosis[J]. Cell, 2011, 145(3): 341-355. |
[10] | 刘俊田. 动脉粥样硬化发病的炎症机制的研究进展[J]. 西安交通大学学报(医学版), 2015,36(2): 141-152. |
[11] | RAITOHARJU E, LYYTIK INEN L P, LEVULA M, et al. miR-21, miR-210, miR-34a, and miR-146a/b are up-regulated in human atherosclerotic plaques in the tampere vascular study[J]. Atherosclerosis, 2011, 219(1): 211-217. |
[12] | VICKERS K C, REMALEY A T. MicroRNAs in atherosclerosis and lipoprotein metabolism.[J]. Current Opinion in Endocrinology Diabetes & Obesity, 2010, 17(2): 150. |
[13] | ZHANG L, HUANG D, WANG Q, et al. MiR-132 inhibits expression of SIRT1 and induces pro-inflammatory processes of vascular endothelial inflammation through blockade of the SREBP-1c metabolic pathway[J]. Cardiovascular Drugs & Therapy, 2014, 28(4): 303. |
[14] | CHOE N, KWON J S, KIM J R, et al. The microRNA miR-132 targets Lrrfip1 to block vascular smooth muscle cell proliferation and neointimal hyperplasia[J]. Atherosclerosis, 2013, 229(2): 348-355. |
[15] | COZZONE D, DEBARD C, Dif N, et al. Activation of liver X receptors promotes lipid accumulation but does not alter insulin action in human skeletal muscle cells[J]. Diabetologia, 2006, 49(5):990-999. |
[16] | CALKIN A C, TONTONOZ P. Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR[J]. Nat Rev Mol Cell Biol, 2012,13(4): 213-224. |
[17] | IVASHCHENKO C Y, Bradley B T, AO Z H, et al. Regulation of the ADMA-DDAH system in endothelial cells: a novel mechanism for the sterol response element binding proteins, SREBP1c and -2[J]. Am J Physiol Heart Circ Physiol, 2010, 298(2): H251-258. |
[18] | MAFFIA P, GRASSIA G, MEGLIO P D, et al. Neutralization of Interleukin-18 inhibits neointimal formation in a rat model of vascular injury[J]. Circulation, 2006, 114(5): 430-437. |