版权说明 帮助中心
首页 > 成果 > 详情

Adaptive homeostasis of the vitamin D–vitamin D nuclear receptor axis in 8-methoxypsoralen-induced hepatotoxicity

认领
导出
Link by DOI
反馈
分享
QQ微信 微博
成果类型:
期刊论文
作者:
GuolinZhao;MuhanadElhafiz;JingweiJiang;DebanjanDas;ZhijianLi;WangZhou;SisiFan;ChanglingWang;ZiqiaoYuan;DengqiuXu;ZhenzhouJiang;LuyongZhang;TaoWang
作者机构:
Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing 210009, China
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China
Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China
Department of Pharmacology and Toxicology Laboratory, Xinjiang Institute of Traditional Uighur Medicine, Urumqi, Xinjiang 830049, China
语种:
中文
关键词:
8-MOP;8-methoxypsoralen;PUVA;8-methoxypsoralen with ultraviolet A radiation (UVA) therapy;VD;vitamin D;VDR;vitamin D receptor;MDR3;multidrug resistance 3 P-glycoprotein;25(OH)D;25-hydroxy vitamin D;γ-GGT;γ-glutamyl transpeptidase;TBIL;total bilirubin;ALT;alanine aminotransferase;LCA;lithocholic acid;Calp;calcipotriol hydrate;VDD;vitamin D-deficient;CLD;conventional lighting and diet;SD;Sprague-Dawley;TBA;total bile acids;ECL;Elecsys electrochemiluminescence;HEK;Human embryonic kidney;Veh;vehicle;hVDR LBD;human VDR ligand-binding domain;ANOVA;one-way analysis of variance;2MV;1,25-dihydroxy vitamin D analog;MTD;maximum tolerant dose;CYP7A1;cholesterol 7 alpha-hydroxylase;MRP3;multidrug resistance-associated protein 3;FXR;farnesoid X receptor;SHP;small heterodimer partner;NR;nuclear receptor;DBD;DNA-binding domain;LBD;ligand-binding domain;8-MOP;Liver injury;Vitamin D;Vitamin D nuclear receptor
期刊:
Toxicology and Applied Pharmacology
ISSN:
0041-008X
年:
2019
卷:
362
页码:
150-158
机构署名:
本校为其他机构
院系归属:
药学院
摘要:
8-methoxypsoralen (8-MOP) with ultraviolet A radiation therapy (PUVA) is the standard therapy for patients with psoriasis, despite the reported potential risks of 8-MOP-induced cholestatic liver injury in both humans and animals. Usually, patients with chronic cholestasis exhibit lower serum 25-hydroxy vitamin D (25(OH)D) levels. But those patients receiving PUVA for psoriasis showed an increase in serum 25(OH)D levels, probably highlighting that the vitamin D–vitamin D nuclear receptor (VD-VDR) axis play a protective role in 8-MOP-induced hepatotoxicity. The present study confirmed 8-MOP could increase serum 25(OH)D levels in conventional lighting and diet (CLD) and vitamin D deficient (VDD) Sprague-Dawley rats. Potential liver risks were also found in CLD and VDD rats after 8-MOP treatment. We proved that 8-MOP could be a potent ligand for VDR using molecular docking and luciferase report assay. Effect of 8-MOP on VDR subcellular distribution was determined using human liver cell line L02. We found 8-MOP could increase VDR protein expression in the nuclear and cytosol extracts and also total cell extracts in L02. siRNAs for VDR were used to determine the role of VDR in protecting 8-MOP-induced cholestasis and potential cellular mechanisms. The results showed 8-MOP could affect the CYP7A1, SHP and MRP3 expression via VDR, and such effects could be reversed by knockdown of VDR expression, suggesting a vital role of VDR involved in 8-MOP-regulated bile acid synthesis and transportation. In conclusion, these results revealed activation of VD–VDR axis may play a beneficial role in 8-MOP-mediated regulation of bile acid synthesis and transportation.

反馈

验证码:
看不清楚,换一个
确定
取消

成果认领

标题:
用户 作者 通讯作者
请选择
请选择
确定
取消

提示

该栏目需要登录且有访问权限才可以访问

如果您有访问权限,请直接 登录访问

如果您没有访问权限,请联系管理员申请开通

管理员联系邮箱:yun@hnwdkj.com