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HDAC2 was involved in placental P-glycoprotein regulation both in vitro and vivo.

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机构： [a]Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China [b]The Cardiac Development and Early Intervention Unit, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China [c]West China Medical School of Sichuan University, Chengdu, Sichuan, China [d]Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China [e]Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education Chengdu, Sichuan, China

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Placental P-glycoprotein (P-gp) plays a significant role in regulating drugs' transplacental transfer rates. Investigations on placental P-gp regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the epigenetic regulation of placental P-gp is rare. Our previous study has demonstrated that HDACs inhibition could up-regulate placental P-gp and HDAC1/2/3 might be involved in this process. The present study was carried out to further explore whether HDAC1/2/3 were indeed involved in the regulation of placental P-gp or not and screen out the subtype engaged in this process. BeWo and JAR cells were transfected with HDAC1/2/3 specific siRNA. After 48 h of transfection, cells were harvested for real-time quantitative PCR (qRT-PCR), Western blot, immunofluorescence and fluorescent dye efflux assay to evaluate P-gp expression, localization, and efflux activity, respectively. Hdac2 siRNA was intraperitoneally injected to pregnant mice every 48 h from E7.5 to E15.5 and digoxin was administered by gavages 1 h prior to euthanasia at E16.5. Placental Hdac1/2/3 and P-gp expression were determined by qRT-PCR and Western blot. Maternal plasma and fetal-unit digoxin concentrations were detected by enzyme-multiplied immunoassay. In vitro, HDAC2 inhibition could significantly elevate P-gp expression and reduce intracellular accumulation of P-gp substrates (DiOC2 (3) and Rh 123) both in BeWo and JAR, while knockdown of HDAC1/3 had no influence on P-gp expression and its efflux activity. Additionally, in vivo, Hdac2 silencing in pregnant mice also elevated placental P-gp expression and decreased digoxin transplacental transfer rate. HDAC2 inhibition could result in induction of placental P-gp expression and functionality both in vitro and in vivo. Copyright © 2017 Elsevier Ltd. All rights reserved.

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出版当年[2017]版：

大类 | 3 区医学

小类 | 2 区妇产科学 3 区发育生物学 3 区生殖生物学

最新[2023]版：

大类 | 2 区医学

小类 | 2 区发育生物学 2 区妇产科学 2 区生殖生物学

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第一作者机构： [a]Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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通讯机构： [a]Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China [*1]Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin- NanLu Road, Chengdu, Sichuan, 610041, China. [*2]Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin- NanLu Road, Chengdu, Sichuan, 610041, China

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