MicroRNA-423-5p reducing the injury of human umbilical vascular endothelial cells induced by lipopolysaccharide through targeting aldehyde dehydrogenase 2

doi:10.16098/j.issn.0529-1356.2020.06.010

Abstract

Abstract:

Objective To investigate the protective effect of microRNA-423-5p(miR-423-5p) on injury of human umbilical vein endothelial cells (HUVECs) induced by lipopolysaccharide(LPS) and its potential mechanism. Methods The HUVECs were induced by 1 mg/L LPS for 24 hours, then expression levels of miR-423-5p and aldehyde dehydrogenasel 2 (ALDH2) in HUVECs induced by LPS were determined by Real-time PCR and Western blotting. The miR-423-5p was down-regulated and ALDH2 was up-regulated by transfected with anti-miR-423-5p and pcDNA-ALDH2. The apoptotic rate of HUVECs was detected by flow cytometry, and the expression levels of Bcl-2 and Bax were measured by Western blotting. The levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in supernatant of HUVECs induced by LPS were determined by the kits. The relationship between miR-423-5p and ALDH2 was validated by dual-luciferase reporter assay system. Results Compared with the control group, LPS induced apoptosis and injury of HUVECs. After LPS induction, the levels of miR-423-5p, Bax, IL-6 and TNF-α in HUVECs increased significantly (P<0.05), and the levels of Bcl-2, ALDH2 mRNA and ALDH2 protein decreased remarkably (P<0.05). Either down-regulation of miR-423-5p or over-expression of ALDH2 alleviated the injury of HUVECs induced by LPS and inhibited apoptosis. MiR-423-5p targeted and negatively regulated the expression of ALDH2. Inhibition of ALDH2 reversed the effects of miR-423-5p down-regulation on the injury of HUVECs induced by LPS.

Conclusion MiR-423-5p alleviates the injury of HUVECs induced by LPS and inhibits apoptosis by targeting ALDH2.

Key words: Umbilical vein endothelial cell, Lipopolysaccharide, MicroRNA-423-5p, Aldehyde dehydrogenase 2, Real-time PCR, Flow cytometry, Human

CLC Number:

R543.6

LIU Wen-fang. MicroRNA-423-5p reducing the injury of human umbilical vascular endothelial cells induced by lipopolysaccharide through targeting aldehyde dehydrogenase 2[J]. Acta Anatomica Sinica, 2020, 51(6): 868-876.

References

［1］ Herrington W, Lacey B, Sherliker P, et al. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease［J］. Circ Res, 2016, 118(4):535-546.
［2］ Zeng JF, Zeng ZL, Zhang K, et al. miR-23b-3p and miR-125b-5p downregulate apo(a) expression by targeting Ets1 in HepG2 cells［J］. Cell Biol Int, 2018, 42(3):313-323.
［3］ Zhang Y. The mechanism research of miR-423-5p regulated human melanocyte oxidative stress injury induced by hydrogen peroxide［D］. Fourth Military Medical University, 2011. (in Chinese)
张莹. miR-423-5p调控过氧化氢诱导下人黑素细胞氧化损伤的机制研究［D］. 第四军医大学, 2011.
［4］ Luo P, Zhang W. Trimetazidine targets microRNA-423-5p signal pathway to protect cardiomyocytes from H2O2-induced apoptosis in ischemic reperfusion injuries［J］. Practical Journal of Clinical Medicine, 2017, 14(4):34-37.(in Chinese)
罗鹏, 张维. 曲美他嗪通过抑制MicroRNA-423-5p凋亡信号通路保护H2O2引起的心肌缺血再灌注损伤［J］. 实用医院临床杂志, 2017, 14(4):34-37.
［5］ Zhu X, Lu X. MiR-423-5p inhibition alleviates cardiomyocyte apoptosis and mitochondrial dysfunction caused by hypoxia/reoxygenation through activation of the wnt/β-catenin signaling pathway via targeting MYBL2［J］. J Cell Physiol, 2019, 234(12):22034-22043.
［6］ Cao RP, Wang WL, Fang TT, et al. Activation of aldehyde dehydrogenase 2 alleviates H2O2-induced injury in cardiomyocytes［J］. Journal of Southern Medical University, 2018, 38(8):938-942.(in Chinese)
曹瑞平, 王文连, 方婷婷, 等. 激活乙醛脱氢酶2的表达可减轻过氧化氢诱导的心肌细胞损伤［J］. 南方医科大学学报, 2018, 38(8):93-942.
［7］ Xu HT, Yu J, Nie GM, et al. ALDH2 attenuates hyperoxia-induced lung epithelial cells injury［J］. Military Medical Journal of South China, 2014, 28(1):34-37.(in Chinese)
徐洪涛, 余健, 聂国明, 等. ALDH2在高氧引起的肺泡上皮细胞损伤中的作用［J］. 华南国防医学杂志, 2014, 28(1):34-37.
［8］ Hu XY, Fang Q, Wang JSh, et al. A preliminary study of improving the function of vascular endothelial cells with high expression of ALDH2 gene［J］. Journal of Guizhou Medical University, 2016, 41(11):1263-1268.(in Chinese)
胡秀英, 方琴, 王季石, 等. 高表达ALDH2基因改善血管内皮细胞功能的初步研究［J］. 贵州医科大学学报, 2016, 41(11):1263-1268.
［9］ Zhou YX, Zhang Ch, Fu HZh, et al. Curcuminoids inhibited LPS-induced vascular endothelial cell injury by down-regulating TLR4/ NF-κB pathway［J］. Central South Pharmacy, 2018, 16(11):23-27.(in Chinese)
周银霞, 张崇, 傅海珍, 等. 姜黄素类组分通过下调TLR4/NF-κB通路抑制LPS诱导的血管内皮细胞损伤［J］. 中南药学, 2018, 16(11):23-27.
［10］ Zhao W, Ma G, Chen X. Lipopolysaccharide induced LOX-1 expression via TLR4/MyD88/ROS activated p38MAPK-NF-κB pathway［J］. Vascul Pharmacol, 2014, 63(3):162-172.
［11］ Tijsen AJ, Creemers EE, Moerland PD, et al. MiR423-5p as a circulating biomarker for heart failure［J］. Circ Res, 2010, 106(6):1035-1039.
［12］ Nabia ek E, Wańha W, Kula D, et al. Circulating microRNAs (mi-423-5p, miR-208a and miR-1) in acute myocardial infarction and stable coronary heart disease［J］. Minerva Cardioangiol, 2013, 61(6):627-637.
［13］ Xu F, Xiang Q, Huang J, et al. Exosomal miR-423-5p mediates the proangiogenic activity of human adipose-derived stem cells by targeting Sufu［J］. Stem Cell Res Ther, 2019, 10(1):106.
［14］ Yang MY, Wang YB, Han B, et al. Activation of aldehyde dehydrogenase 2 slows down the progression of atherosclerosis via attenuation of ER stress and apoptosis in smooth muscle cells［J］. Acta Pharmacol Sin, 2018, 39(1):48-58.
［15］ Zhang Y, Ren J. Aldehyde dehydrogenase 2 (ALDH2) rescues myocardial ischaemia/reperfusion injury: role of autophagy paradox and toxic aldehyde［J］. Eur Heart J, 2011, 32(8):1025-1038.
［16］ Lin W, Xia JL, Wang Y. Effect of uremic toxin sulfate p-cresol on vascular endothelial cells in vitro ［J］. Acta Anatomica Sinica, 2014,45 (2): 216-220.(in Chinese)
林伟,夏剑岚,王毅.尿毒症毒素硫酸盐对甲酚对血管内皮细胞的体外作用［J］.解剖学报,2014,45(2):216-220.

[1]	XIE Hui-lan FANG Fang LIN Yi. Mechanism of Chir99021 regulating Wnt/β-catenin signaling pathway inhibiting osteogenic differentiation of rat dental pulp stem cells [J]. Acta Anatomica Sinica, 2024, 55(1): 67-72.
[2]	ZHENG Li-ping LIU Xia DU Xiao-hua WU Ya-juan LIU Shan-shan . Expression and distribution of brain-derived neurotrophic factor in different cerebrum regions of yak and cattle [J]. Acta Anatomica Sinica, 2024, 55(1): 10-16.
[3]	ZHAO Wei-ming LI Xiao YU Guo-ying WANG Gai-ping CHANG Cui-fang . Effect of serine protease inhibitor Kazaltype 1 on the proliferation of hepatocellular carcinoma cell and its mechanism [J]. Acta Anatomica Sinica, 2023, 54(6): 695-702.
[4]	ZHANG Qin YANG Jun-xia JIANG Qing-song. Effect of fosinopril on angiotensin converting enzyme 2 and vascular endothelial growth factor in diabetic retinopathy mice [J]. Acta Anatomica Sinica, 2023, 54(6): 628-634.
[5]	HE Ke-ke LI Yuan-di WEN Ting-hao ZHU Jie GAO Jie HU Rong HAN Feng SU Min . Erythrocyte membrane-associated protein inhibiting Th17 cell differentiation via IL-6/STAT3/ROR-γt signaling pathway in experimental autoimmune encephalomyelitis mice encephalomyelitis mice [J]. Acta Anatomica Sinica, 2023, 54(5): 538-545.
[6]	LIU Yan-jing SHI Yong-hong . Automatic extraction of point cloud on cartilage surface of intraoperative knee using FPFH-PointNet [J]. Acta Anatomica Sinica, 2023, 54(5): 553-559.
[7]	YU Hua-jing WEI Lu-yang LIU Shan-shan GUAN Cheng-jian ZHANG Zhong-tao. Role and clinical significance of MLLT1 super elongation complex subunit in the occurrence and development of hepatocellular carcinoma [J]. Acta Anatomica Sinica, 2023, 54(4): 425-433.
[8]	YAO Xiao-xiao LIU Xiao-li LI Ru-hua LI Chang-sheng REN Chuan-gen CHEN Cheng-chun . Susceptibility weighted imaging of superficial cerebellar veins [J]. Acta Anatomica Sinica, 2023, 54(4): 465-472.
[9]	JI Rui-jie LI Wen JIN Guo-hua ZHANG Xin-hua. Expression and effect of roundabout guidance receptor 1 during valproate induced neural stem cells differentiation [J]. Acta Anatomica Sinica, 2023, 54(3): 255-260.
[10]	LI Wei WANG Li WANG Zhi-hua LIU Qing-chun HAN Rong-sheng . Long non-coding RNA alpha-2-macroglobulin antisense RNA 1 regulating oxidized low density lipoprotein-induced human brain microvascular endothelial cell damage by targeting microRNA-106b-5p [J]. Acta Anatomica Sinica, 2023, 54(3): 319-327.
[11]	LI Guang LI Jie ZHANG Ping . Mechanism of microRNA-30d-5p regulating osteogenic differentiation of bone marrow stromal cells through glucose-regulated 78 [J]. Acta Anatomica Sinica, 2023, 54(2): 195-201.
[12]	LIU Xia ZHENG Li-ping DU Xiao-hua WANG Yu-jiao WU Ya-juan . Expression and localization of neuroglobin in the brain tissue of Saiga antelope [J]. Acta Anatomica Sinica, 2023, 54(2): 188-194.
[13]	SUN Meng-fang CHENG Yi-sheng WANG Feng JIN Meng-hao WANG De-xiu. Effect of bergapten on glucose and oxygen deprivation induced PC12 cell injury by regulating long non-coding RNA opioid receptor gene expression [J]. Acta Anatomica Sinica, 2023, 54(1): 56-62.
[14]	DUAN Qian LI Jian-hua LI Wen-jia WANG Ru WU Zhen YUAN Ming. Molecular analysis of interleukin 10 promoter region-592A/C polymorphism in hypertensive disorders of pregnancy in Qinghai Han nationality [J]. Acta Anatomica Sinica, 2023, 54(1): 63-69.
[15]	LI Qiao LIU Xia DU Xiao-hua MI Xiao-yu WEN Yong-qiang FANG Ying-dong . Expression and localization of vascular endothelial growth factor-B in diencephalon and brainstem related tissues of the Yak’s brain [J]. Acta Anatomica Sinica, 2023, 54(1): 30-35.