Growth arrest-specific protein-6/AXL signaling induces preeclampsia in rats†.

Abstract:
:Preeclampsia (PE) is a complicated obstetric complication characterized by increased blood pressure, decreased trophoblast invasion, and inflammation. The growth arrest-specific 6 (Gas6) protein is known to induce dynamic cellular responses and is elevated in PE. Gas6 binds to the AXL tyrosine kinase receptor and AXL-mediated signaling is implicated in proliferation and migration observed in several tissues. Our laboratory utilized Gas6 to induce preeclamptic-like conditions in pregnant rats. Our objective was to determine the role of Gas6/AXL signaling as a possible model of PE. Briefly, pregnant rats were divided into three groups that received daily intraperitoneal injections (from gestational day 7.5 to 17.5) of phosphate buffered saline (PBS), Gas6, or Gas6 + R428 (an AXL inhibitor administered from gestational day 13.5 to 17.5). Animals dispensed Gas6 experienced elevated blood pressure, increased proteinuria, augmented caspase-3-mediated placental apoptosis, and diminished trophoblast invasion. Gas6 also enhanced expression of several PE-related genes and a number of inflammatory mediators. Gas6 further enhanced placental oxidative stress and impaired mitochondrial respiration. Each of these PE-related characteristics was ameliorated in dams and/or their placentae when AXL inhibition by R428 occurred in tandem with Gas6 treatment. We conclude that Gas6 signaling is capable of inducing PE and that inhibition of AXL prevents disease progression in pregnant rats. These results provide insight into pathways associated with PE that could be useful in the clarification of potential therapeutic approaches.
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BIOLOGY OF REPRODUCTION
BIOL REPROD
最新影响因子:4.161 | 期刊ISSN:0006-3363 | CiteScore:2.88 |
出版周期:Monthly | 是否OA:YES | 出版年份:1969 |
期刊官方网址:http://www.biolreprod.org/
自引率:7.40% | 研究方向:生物-生殖生物学 |
出版地区:UNITED STATES |
SCI期刊coverage:Science Citation Index Expanded(科学引文索引扩展)
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BIOLOGY OF REPRODUCTION 期刊简介
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Covers current research relating to all aspects of the biology of reproduction.
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大类(学科) | 小类(学科) | 学科排名 |
医学 |
REPRODUCTIVE BIOLOGY(生殖生物学) 2区 |
5/29 |
最新公布的期刊年发文量
年度总发文量 | 年度论文发表量 | 年度综述发表量 |
183 | 168 | 15 |
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872篇文献
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1 |
大类(学科):Medicine
小类(学科):Reproductive Medicine
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#0/64
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2 |
大类(学科):Biochemistry, Genetics and Molecular Biology
小类(学科):Cell Biology
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#126/264
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