|Self-Control of HGF Regulation on Human Trophoblast Cell Invasion via Enhancing c-Met Receptor Shedding by ADAM10 and ADAM17|
|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|
|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|
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)
|项目编号||2011CB944400 ; 2010CB535015 ; 81025004 ; KSCX2-EW-R-06|
|资助机构||Chinese National Special Fund ; National Natural Sciences Foundation ; Innovation Program in Chinese Academy of Sciences|
|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
|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.|
|APA||Yang, Yanyan.,Wang, Yongqing.,Zeng, Xin.,Ma, Xiao-jie.,Zhao, Yangyu.,...&Wang, Yan-ling.(2012).Self-Control of HGF Regulation on Human Trophoblast Cell Invasion via Enhancing c-Met Receptor Shedding by ADAM10 and ADAM17.JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,97(8),E1390-E1401.|
|MLA||Yang, Yanyan,et al."Self-Control of HGF Regulation on Human Trophoblast Cell Invasion via Enhancing c-Met Receptor Shedding by ADAM10 and ADAM17".JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 97.8(2012):E1390-E1401.|