Role of OATP1B3 in the transport of bile acids assessed using first-trimester trophoblasts.

Abstract

AIMS:

The aim of this study was to investigate the transport of two kinds of bile acids by organic anion transporting polypeptide 1B3 (OATP1B3) using first-trimester trophoblasts. The mechanisms of damage to fetuses with intrahepatic cholestasis of pregnancy were investigated, providing new potential strategies for targeted therapies aimed at reducing fetal risk.

MATERIAL AND METHODS:

The expression of OATP1B3 was knocked down by lentiviral vector-mediated RNA interference, and silencing efficiency was assessed using real-time polymerase chain reaction and Western blotting. The cytotoxicity of two bile acids (glycocholic acid [GCA] and glycochenodeoxycholic acid [GCDCA]) was assessed using the MTT method. Transport of bile acids was assessed by establishing an in vitro trophoblast monolayer model using polyester Transwell-clear inserts, and the concentration of bile acids in the upper compartment was assessed using high-pressure liquid chromatography.

RESULTS:

GCA and GCDCA (10 and 20 μM) were not cytotoxic to the SWAN cell line (P > 0.05). RNAi treatment decreased the mRNA and protein expressions of OATP1B3 by 94.42% and 49.51%, respectively (P < 0.05). The bile acid transport curves were similar in the control and negative RNAi groups, whereas those in the RNAi group differed significantly from those in the control and negative RNAi groups. The concentration of GCA and GCDCA in the upper compartment was significantly lower in the RNAi group than in the control and negative RNAi groups.

CONCLUSIONS:

OATP1B3 expression in trophoblasts was confirmed indirectly by its ability to transport the bile acids GCA and GCDCA.

• Authors: Ziru Yan, Eqiong Li, Lingfei He, Jianhua Wang, Xiaojun Zhu, Hanzhi Wang, Zhengping Wang
• Journal: The journal of obstetrics and gynaecology research (J Obstet Gynaecol Res) Vol. 41 Issue 3 Pg. 392-401 (Mar 2015) ISSN: 1447-0756 [Electronic] Australia
• PMID: 25345542 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Chemical References

• Organic Anion Transporters, Sodium-Independent
• RNA, Messenger
• SLCO1B3 protein, human
• Solute Carrier Organic Anion Transporter Family Member 1B3
• Glycochenodeoxycholic Acid
• Glycocholic Acid

Topics

• Biological Transport
• Cell Survival (drug effects)
• Cells, Cultured
• Cholestasis, Intrahepatic (metabolism)
• Female
• Gene Knockdown Techniques
• Glycochenodeoxycholic Acid (pharmacokinetics, pharmacology)
• Glycocholic Acid (pharmacokinetics, pharmacology)
• Humans
• Organic Anion Transporters, Sodium-Independent (genetics, metabolism)
• Pregnancy
• Pregnancy Complications (metabolism)
• Pregnancy Trimester, First
• RNA, Messenger (metabolism)
• Solute Carrier Organic Anion Transporter Family Member 1B3
• Trophoblasts (metabolism)