已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Organic Anion Transporting Polypeptide 2B1 in Human Fetal Membranes: A Novel Gatekeeper for Drug Transport During Pregnancy?

有机阳离子转运蛋白 胎儿 溶质载体族 胎盘 怀孕 有机阴离子转运多肽 药理学 化学 生物 医学
作者
Esha Ganguly,Ananth K. Kammala,Meagan Benson,Lauren Richardson,Arum Han,Ramkumar Menon
出处
期刊:Frontiers in Pharmacology [Frontiers Media]
卷期号:12 被引量:1
标识
DOI:10.3389/fphar.2021.771818
摘要

Current intervention strategies have not been successful in reducing the risks of adverse pregnancy complications nor maternal and fetal morbidities associated with pregnancy complications. Improving pregnancy and neonatal outcomes requires a better understanding of drug transport mechanisms at the feto-maternal interfaces, specifically the placenta and fetal membrane (FM). The role of several solute carrier uptake transporter proteins (TPs), such as the organic anion transporting polypeptide 2B1 (OATP2B1) in transporting drug across the placenta, is well-established. However, the mechanistic role of FMs in this drug transport has not yet been elucidated. We hypothesize that human FMs express OATP2B1 and functions as an alternate gatekeeper for drug transport at the feto-maternal interface. We determined the expression of OATP2B1 in term, not-in-labor, FM tissues and human FM cells [amnion epithelial cell (AEC), chorion trophoblast cell (CTC), and mesenchymal cells] using western blot analyses and their localization using immunohistochemistry. Changes in OATP2B1 expression was determined for up to 48 h after stimulation with cigarette smoke extract (CSE), an inducer of oxidative stress. The functional role of OATP2B1 was determined by flow cytometry using a zombie violet dye substrate assay. After OATP2B1 gene silencing, its functional relevance in drug transport through the feto-maternal interface was tested using a recently developed feto-maternal interface organ-on-a-chip (OOC) system that contained both FM and maternal decidual cells. Propagation of a drug (Rosuvastatin, that can be transported by OATP2B1) within the feto-maternal interface OOC system was determined by mass spectrometry. FMs express OATP2B1 in the CTC and AEC layers. In FM explants, OATP2B1 expression was not impacted by oxidative stress. Uptake of the zombie violet dye within AECs and CTCs showed OATP2B1 is functionally active. Silencing OATP2B1 in CTCs reduced Rosuvastatin propagation from the decidua to the fetal AEC layer within the feto-maternal interface-OOC model. Our data suggest that TPs in FMs may function as a drug transport system at the feto-maternal interface, a function that was previously thought to be performed exclusively by the placenta. This new knowledge will help improve drug delivery testing during pregnancy and contribute to designing drug delivery strategies to treat adverse pregnancy outcomes.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
AswinnLyu完成签到,获得积分10
4秒前
4秒前
overlord完成签到,获得积分10
5秒前
顾矜应助小蛇玩采纳,获得10
5秒前
星辰大海应助WangZ采纳,获得10
9秒前
郑总完成签到 ,获得积分10
14秒前
潇洒斑马完成签到,获得积分10
16秒前
20秒前
Simone完成签到,获得积分10
21秒前
22秒前
量子星尘发布了新的文献求助10
23秒前
23秒前
鱼yu发布了新的文献求助10
26秒前
27秒前
冷静的忆秋完成签到,获得积分10
28秒前
大只佬发布了新的文献求助10
29秒前
小蛇玩发布了新的文献求助10
29秒前
wangx发布了新的文献求助10
30秒前
QF发布了新的文献求助10
31秒前
31秒前
31秒前
34秒前
Simone发布了新的文献求助10
35秒前
LiuJ完成签到 ,获得积分10
35秒前
seven发布了新的文献求助10
35秒前
36秒前
科研通AI5应助ls采纳,获得10
37秒前
40秒前
42秒前
43秒前
量子星尘发布了新的文献求助10
43秒前
科研通AI5应助iqa采纳,获得10
45秒前
peanut完成签到 ,获得积分10
46秒前
欣论完成签到 ,获得积分10
47秒前
TBI发布了新的文献求助10
48秒前
50秒前
51秒前
正直的大树完成签到 ,获得积分10
55秒前
科研一霸发布了新的文献求助10
55秒前
量子星尘发布了新的文献求助10
55秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2700
Neuromuscular and Electrodiagnostic Medicine Board Review 1000
Statistical Methods for the Social Sciences, Global Edition, 6th edition 600
こんなに痛いのにどうして「なんでもない」と医者にいわれてしまうのでしょうか 510
ALUMINUM STANDARDS AND DATA 500
Walter Gilbert: Selected Works 500
An Annotated Checklist of Dinosaur Species by Continent 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3666266
求助须知:如何正确求助?哪些是违规求助? 3225307
关于积分的说明 9762401
捐赠科研通 2935195
什么是DOI,文献DOI怎么找? 1607513
邀请新用户注册赠送积分活动 759223
科研通“疑难数据库(出版商)”最低求助积分说明 735185