CCN3 (NOV): Key regulator promoting cell cycle exit and migration of trophoblast cells into the maternal compartment

CCN3 (NOV)：促进细胞周期退出和滋养层细胞迁移至母体室的关键调节因子

• 批准号: 246503793
• 负责人: Professorin Dr. Alexandra Gellhaus
• 金额: --
• 依托单位: Universitätsklinik für Frauenheilkunde und Geburtshilfe
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/246503793?language=en
• 关键词: CCN3; NOV; Key; regulator; promoting

Appropriate placentation relies on the capacity of first trimester EVT cells to proliferate and then to invade into the maternal tissue after having escaped from the cell cycle. Changes in this highly coordinated programme could lead to the pregnancy disease preeclampsia characterized by trophoblast hypoinvasion and defective vascular remodeling.We have shown that the matricellular protein CCN3 contributes to the regulation of the switch from the proliferating trophoblast of the cell column to the non-proliferating phenotype invading the decidua and the spiral arteries during placental development by causing a G0/G1 cell cycle arrest as well as enhancing migration properties. The cell cycle arrest is accompanied by an increased expression of activated Notch1 and its target gene p21. At the same time CCN3 increases migration properties of trophoblast cells by an activation of FAK and Akt pathways via integrins.In this proposed study we want to investigate more precisely the detailed molecular mechanisms how CCN3 regulates the G0/G1 cell cycle arrest and how the migration can be triggered at the same time to fulfil a successful placental development. Moreover, we would like to identify impaired signaling cascades mediated by CCN3 for proliferation and / or migration properties in early-onset preeclampsia.

适当的胎盘形成依赖于妊娠早期EVT细胞的增殖能力，然后在脱离细胞周期后侵入母体组织。在这个高度协调的程序的变化可能会导致妊娠疾病先兆子痫的特点是滋养层低侵袭和缺陷的血管重塑。我们已经表明，基质细胞蛋白CCN 3有助于调节开关从增殖的滋养细胞的细胞柱的非增殖表型侵入蜕膜和螺旋动脉在胎盘发育过程中，通过引起G 0/G1细胞周期阻滞以及增强迁移特性。细胞周期停滞伴随着活化的Notch 1及其靶基因p21的表达增加。同时，CCN 3通过整合素激活FAK和Akt信号通路，增加滋养层细胞的迁移特性，我们希望更精确地研究CCN 3如何调控G 0/G1细胞周期阻滞以及如何同时触发迁移以实现成功的胎盘发育的详细分子机制。此外，我们想确定受损的信号级联CCN 3介导的增殖和/或迁移特性在早发性先兆子痫。

项目成果

Increased Rat Placental Fatty Acid, but Decreased Amino Acid and Glucose Transporters Potentially Modify Intrauterine Programming

大鼠胎盘脂肪酸增加，但氨基酸和葡萄糖转运蛋白减少可能会改变宫内编程

• DOI: 10.1002/jcb.25450
• 发表时间: 2016
• 期刊: Journal of Cellular Biochemistry
• 影响因子: 4
• 作者: Nüsken E;Gellhaus A;Kühnel E;Swoboda I;Wohlfarth M;Vohlen C;Schneider H;Dötsch J;Nüsken KD
• 通讯作者: Nüsken KD

CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties

• DOI: 10.1080/19336918.2016.1139265
• 发表时间: 2016-01
• 期刊: Cell Adhesion & Migration
• 影响因子: 3.2
• 作者: Friederike Kipkeew;Manuela Kirsch;D. Klein;M. Wuelling;E. Winterhager;A. Gellhaus

Human sFLT1 Leads to Severe Changes in Placental Differentiation and Vascularization in a Transgenic hsFLT1/rtTA FGR Mouse Model

• DOI: 10.3389/fendo.2019.00165
• 发表时间: 2019-03-21
• 期刊: FRONTIERS IN ENDOCRINOLOGY
• 影响因子: 5.2
• 作者: Vogtmann, Rebekka;Kuehnel, Elisabeth;Gellhaus, Alexandra
• 通讯作者: Gellhaus, Alexandra

Soluble B7‐H4 blood serum levels are elevated in women at high risk for preeclampsia in the first trimester, as well as in patients with confirmed preeclampsia

• DOI: 10.1111/aji.12988
• 发表时间: 2018-09
• 期刊: American Journal of Reproductive Immunology
• 影响因子: 3.6
• 作者: P. Mach;Luisa Nolte-Boenigk;L. Droste;L. Fox;M. Frank;B. Schmidt;F. Herse;S. Verlohren;L. Wicherek;A. Iannaccone;C. Birdir;D. Andrikos;R. Kimmig;A. Gellhaus;A. Köninger

A double-hit pre-eclampsia model results in sex-specific growth restriction patterns

• DOI: 10.1242/dmm.035980
• 发表时间: 2019-02-01
• 期刊: DISEASE MODELS & MECHANISMS
• 影响因子: 4.3
• 作者: Stojanovska, Violeta;Dijkstra, Dorieke J.;Plosch, Torsten
• 通讯作者: Plosch, Torsten