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LncRNA H19 Regulates P-glycoprotein Expression Through the NF-κB Signaling Pathway in the Model of Status Epilepticus
被引:6
作者:
Xie, Yangmei
[1
]
Wang, Ming
[1
]
Shao, Yiye
[2
]
Chen, Yinghui
[1
]
机构:
[1] Fudan Univ, Huashan Hosp, Dept Neurol, 12 Wulumuqi Rd, Shanghai 200040, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Neurol, Sch Med, Shanghai 200940, Peoples R China
基金:
中国国家自然科学基金;
关键词:
Status epilepticus;
P-glycoprotein;
lncNRA;
H19;
NF-kappa B signaling pathway;
ceRNA;
LONG NONCODING RNA;
REFRACTORY STATUS EPILEPTICUS;
BLOOD-BRAIN-BARRIER;
DRUG-RESISTANCE;
EFFLUX TRANSPORTER;
SEIZURE;
INFLAMMATION;
MECHANISMS;
HYPOTHESIS;
INCREASE;
D O I:
10.1007/s11064-022-03803-w
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Pharmaco-resistance is a challenging problem for treatment of status epilepticus (SE) in the clinic. P-glycoprotein (P-gp) is one of the most important multi-drug transporters that contribute to drug resistance of SE. Long noncoding RNAs (lncRNAs) have been increasingly recognized as versatile regulators of P-gp in tumors and epilepsy. However, the function of lncRNAs in drug resistance of SE remains largely unknown. In the present study, pilocarpine-induced rat model is used to explore the expression profiles of lncRNAs in the hippocampus of SE using RNA sequencing. Our results implied that the level of lncRNA H19 was significantly increased in the hippocampus of SE rats, which was positively correlated with the level of P-gp. While downregulation of H19 could inhibit the expression of P-gp and alleviate neural damage in the hippocampus of SE rats. Furthermore, it was revealed that H19 regulates P-gp expression through the nuclear factor-kappaB (NF-kappa B) signaling pathway by functioning as a competing endogenous RNA against microRNA-29a-3p. Overall, our study indicated that H19 regulates P-gp expression and neural damage induced by SE through the NF-kappa B signaling pathway, which provides a promising target to overcome drug resistance and alleviate brain damage for SE.
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页码:929 / 941
页数:13
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