期刊
PLACENTA
卷 30, 期 4, 页码 361-367出版社
W B SAUNDERS CO LTD
DOI: 10.1016/j.placenta.2009.01.004
关键词
Placenta; Leptin; System A amino acid transporter; STAT3
资金
- National Institutes of Health [P01-HD30367]
- Pennsylvania Department of Health
- Magee-Women's Research Institute Foundation
- Faculty of Medicine
- RWTH Aachen University, Germany
Background: Amino acids are important nutrients during fetal development, and the activity of placental amino acid transporters is crucial in the regulation of fetal growth. Leptin, an adipocyte- and placenta-derived hormone, has been proposed to act as a peripheral signal in reproduction in humans. Leptin is elevated during pregnancy and elevated further in pathologic pregnances Such as preeclampsia. However, the role of leptin in placental function has not been fully elucidated. We hypothesize that: leptin plays a role in the regulation of placental amino acid transport by activation of the JAK-STAT pathway. Methods: Placental amino acid transport, specifically system A transport was studied in placental villous fragments using the amino acid analog, methylaminoisobutyric acid (MeAIB). Specific inhibitors of the JAK-STAT signal transduction pathway were used to further elucidate their role in leptin-mediated effects on amino acid transport activity. Western blotting was performed to identify STAT3 phosphorylation as a measure of leptin receptor activation. Results: Leptin significantly increased system A amino acid transporter activity by 22-42% after I h of incubation. Leptin activated JAK-STAT signaling pathway as evidenced by STAT3 phosphorylation, and inhibition of STAT3 or JAK2 resulted in 36-45% reduction in system A amino acid transporter activity. Furthermore, blocking endogenously produced leptin also decreased system A transport by 45% comparable to STAT3 inhibition. Conclusions: These data demonstrate that leptin stimulates system A by JAK-STAT TAT dependent pathway in placental villous fragments. Our findings support the autocrine/paracrine role of leptin in regulating amino acid transport in the human placenta. (C) 2009 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据