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Modulation of Placental Breast Cancer Resistance Protein by HDAC1 in Mice: Implications for Optimization of Pharmacotherapy During Pregnancy.

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机构： [1]Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, No. 20, Section 3, RenminNanLu Road, Chengdu 610041, Sichuan, China [2]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 [3]Department of Pediatric Rehabilitation, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China [4]Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China [5]Key Laboratory of Development and Diseases of Women and Children of Sichuan Province, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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关键词： Placenta Breast cancer resistance protein HDAC1 Pharmacotherapy Gestation Epigenetic regulation

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Breast cancer resistance protein (BCRP/ABCG2) is a critical drug efflux transporters by limiting drugs' transplacental transfer rates. More investigations on the regulation of placental BCRP offer great promise for enabling pronounced progress in individualized and safe pharmacotherapy during pregnancy. Histone deacetylases (HDACs) play an important role in epigenetic regulation of placental genes. It was reported recently by us that HDAC1 was involved in placental BCRP regulation in vitro. The aim of this study was to further explore the effect of HDAC1 on placental BCRP expression and functionality in animals. Randomly assigned C57BL pregnant dams received intraperitoneal injections of a negative control siRNA or Hdac1 siRNA from embryonic day 7.5 (E7.5) to E15.5, respectively. At E16.5, glyburide (GLB), a probe for evaluating placental BCRP efflux functionality, was injected via the tail vein. Animals were sacrificed through cervical dislocation at various times (5-180 min) after drug administration. The maternal blood, placentas, and fetal-units were collected. GLB concentrations were determined by a validated high-performance liquid chromatography/mass spectrometry (HPLC-MS) assay. Real-time quantitative PCR (qRT-PCR), Western blot, and immunohistochemical (IHC) analysis were employed to identify mRNA/protein levels and localization of gene expressions, respectively. It was noted that Hdac1 inhibition significantly decreased placental Bcrp expression, with markedly increases of GLB concentrations and area under the concentration-time curve (AUC) in fetal-units. Particularly, the ratios of fetal-unit/maternal plasma GLB concentrations were also significantly elevated following Hdac1 repression. Taken together, these findings suggested that HDAC1 was involved in positive regulation of placental BCRP expression and functionality in vivo.© 2021. The Author(s).

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出版当年[2021]版：

大类 | 3 区医学

小类 | 3 区妇产科学 4 区生殖生物学

最新[2023]版：

大类 | 3 区医学

小类 | 4 区妇产科学 4 区生殖生物学

第一作者：

第一作者机构： [1]Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, No. 20, Section 3, RenminNanLu Road, Chengdu 610041, Sichuan, China [2]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

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通讯机构： [1]Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, No. 20, Section 3, RenminNanLu Road, Chengdu 610041, Sichuan, China [2]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

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Modulation of Placental Breast Cancer Resistance Protein by HDAC1 in Mice: Implications for Optimization of Pharmacotherapy During Pregnancy.

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