Silencing microRNA-143 protects the integrity of the blood-brain barrier: implications for methamphetamine abuse

被引：75

作者：

Bai, Ying ^{[1
]}

Zhang, Yuan ^{[1
]}

Hua, Jun ^{[2
]}

Yang, Xiangyu ^{[3
]}

Zhang, Xiaotian ^{[1
]}

Duan, Ming ^{[4
]}

Zhu, Xinjian ^{[1
]}

Huang, Wenhui ^{[5
]}

Chao, Jie ^{[6
]}

Zhou, Rongbin ^{[7
,8
,9
]}

Hu, Gang ^{[2
]}

Yao, Honghong ^{[1
,3
]}

机构：

[1] Southeast Univ, Sch Med, Dept Pharmacol, Nanjing, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Dept Pharmacol, Jiangsu Key Lab Neurodegenerat, 140 Hanzhong Rd, Nanjing, Jiangsu, Peoples R China

[3] Southeast Univ, Inst Life Sci, Key Lab Dev Genes & Human Dis, Nanjing, Jiangsu, Peoples R China

[4] Jilin Univ, Inst Zoonosis, Virosis Lab, Minist Educ,Key Lab Zoonosis, 5333 Xi An Rd, Changchun 130062, Peoples R China

[5] Univ Saarland, Dept Mol Physiol, Ctr Integrat Physiol & Mol Med, D-66421 Homburg, Germany

[6] Southeast Univ, Sch Med, Dept Physiol, Nanjing, Jiangsu, Peoples R China

[7] Univ Sci & Technol China, Inst Immunol, Hefei, Peoples R China

[8] Univ Sci & Technol China, CAS Key Lab Innate Immun & Chron Dis, Sch Life Sci, Hefei, Peoples R China

[9] Univ Sci & Technol China, Med Ctr, Hefei, Peoples R China

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

中国国家自然科学基金;

关键词：

SMOOTH-MUSCLE-CELLS; ENDOTHELIAL-CELLS; GROWTH-FACTOR; PUMA; DISRUPTION; APOPTOSIS; ACTIVATION; INDUCTION; GENE; EXPRESSION;

D O I：

10.1038/srep35642

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

MicroRNA-143 (miR-143) plays a critical role in various cellular processes; however, the role of miR-143 in the maintenance of blood-brain barrier (BBB) integrity remains poorly defined. Silencing miR-143 in a genetic animal model or via an anti-miR-143 lentivirus prevented the BBB damage induced by methamphetamine. miR-143, which targets p53 unregulated modulator of apoptosis (PUMA), increased the permeability of human brain endothelial cells and concomitantly decreased the expression of tight junction proteins (TJPs). Silencing miR-143 increased the expression of TJPs and protected the BBB integrity against the effects of methamphetamine treatment. PUMA overexpression increased the TJP expression through a mechanism that involved the NF-kappa B and p53 transcription factor pathways. Mechanistically, methamphetamine mediated up-regulation of miR-143 via sigma-1 receptor with sequential activation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3' kinase (PI3K)/Akt and STAT3 pathways. These results indicated that silencing miR-143 could provide a novel therapeutic strategy for BBB damage-related vascular dysfunction.

引用

页数：15

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