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学科主题: 临床医学
题名:
Self-Control of HGF Regulation on Human Trophoblast Cell Invasion via Enhancing c-Met Receptor Shedding by ADAM10 and ADAM17
作者: Yang, Yanyan1,3; Wang, Yongqing2; Zeng, Xin1; Ma, Xiao-jie1; Zhao, Yangyu2; Qiao, Jie2; Cao, Bin1,3; Li, Yu-xia1; Ji, Lei1; Wang, Yan-ling1
刊名: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
发表日期: 2012-08-01
DOI: 10.1210/jc.2012-1150
卷: 97, 期:8, 页:E1390-E1401
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Endocrinology & Metabolism
研究领域[WOS]: Endocrinology & Metabolism
关键词[WOS]: HEPATOCYTE GROWTH-FACTOR ; FACTOR SCATTER FACTOR ; OXIDATIVE STRESS ; HUMAN PLACENTA ; TYROSINE KINASE ; PROTOONCOGENE PRODUCT ; FACTOR/SCATTER FACTOR ; PREECLAMPSIA ; EXPRESSION ; PROTEIN
英文摘要:

Context: Hepatocyte growth factor (HGF)/c-Met signaling has been implicated in mammalian placental development. Integral c-Met can be released from endothelial cell membrane by proteolysis to form a soluble, truncated protein [soluble Met (sMet)], which is biochemically able to bind HGF and may disrupt HGF/c-Met signaling. By far, production of sMet in human placenta has not been reported, and the shedding mechanism remains unclear.

Objectives and Design: In this study, production of sMet in healthy pregnant placenta and preeclamptic ones was compared, and the role of sMet on trophoblast cell invasion as well as the regulation of c-Met shedding by HGF were investigated in an immortal trophoblast cell line, B6Tert-1.

Results: Placenta productions of sMet, pro- and active forms of a disintegrin and metalloprotease 10 (ADAM10) and ADAM17 in preeclamptic patients were significantly higher than those in normal pregnant women. In B6Tert-1 cells, the HGF-induced promotion on cell invasion and activation of MAPK and AKT could be extensively blocked by sMet. ADAM10 and ADAM17, but not ADAM12, were explored to be sheddases of c-Met. HGF down-regulated c-Met receptor expression, whereas it up-regulated pro- and active/mature forms of ADAM10 and ADAM17 expression, which resulted in enhanced sMet production. Stimulation of H2O2 caused an increase in active ADAM10, pro-ADAM17, and active ADAM17 levels and thus excessive c-Met shedding.

Conclusions: HGF could negatively self-control its regulatory effect on trophoblast cell invasion via enhancing proteolysis of its receptor. Unbalancing of HGF self-control by oxidative stress may lead to impeding placentation in relevance to preeclampsia. (J Clin Endocrinol Metab 97: E1390-E1401, 2012)

语种: 英语
所属项目编号: 2011CB944400 ; 2010CB535015 ; 81025004 ; KSCX2-EW-R-06
项目资助者: Chinese National Special Fund ; National Natural Sciences Foundation ; Innovation Program in Chinese Academy of Sciences
WOS记录号: WOS:000307457400006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55104
Appears in Collections:北京大学第三临床医学院_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China
2.Peking Univ, Hosp 3, Dept Obstet & Gynecol, Beijing 100191, Peoples R China
3.Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China

Recommended Citation:
Yang, Yanyan,Wang, Yongqing,Zeng, Xin,et al. Self-Control of HGF Regulation on Human Trophoblast Cell Invasion via Enhancing c-Met Receptor Shedding by ADAM10 and ADAM17[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,2012,97(8):E1390-E1401.
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