TGFβ-mediated RhoA expression is necessary for epithelial-mesenchymal transition in the embryonic chick heart
TGFβ-mediated RhoA expression is necessary for epithelial-mesenchymal transition in the embryonic chick heart
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DOI：
10.1002/dvdy.20771
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发表时间：
2006-06-01
影响因子：
2.5
通讯作者：
Kitten, Gregory T.
中科院分区：
文献类型：
--
作者：
Tavares, Andre Luiz P.;Mercado-Pimentel, Melania E.;Kitten, Gregory T.
胚胎心脏的房室管(AVC)内皮细胞经历上皮-间充质转化(EMT)，并向细胞外基质迁移。我们在这里探讨RhoA是否参与了这种EMT。在所研究的阶段，RhoA在雏鸡心脏的所有细胞中都被检测到。当。EMT正在积极进行。在胶原凝胶培养中，C3胞外酶处理的组织块间充质细胞数量明显减少。用siRNA抑制RhoA基因的表达，激活的内皮细胞和间充质细胞均明显减少。RhoA的缺失导致Rhol1、Cyclin-b2和β-catenin信息的减少，表明这些基因在RhoA下游受到调控。相比之下，RUNX-2并没有减少。抑制转化生长因子β3或转化生长因子β2活性可显著降低RhoA信使。这些数据将RhoA置于转化生长因子β调节的内皮激活和间质侵袭的通路中，并证明了EMT过程中的功能需求。
Endothelia in the atrioventricular canal (AVC) of the embryonic heart undergo an epithelial-mesenchymal transition (EMT) and migrate into the underlying extracellular matrix. We explore here whether RhoA mediates this EMT. RhoA was detected in all cells of the chick heart during the stages studied. Expression was elevated when. EMT was actively occurring. Explants treated with C3 exoenzyme in collagen gel cultures showed a significant decrease in mesenchymal cell numbers. siRNA was used to inhibit RhoA mRNA, and both activated endothelial and mesenchymal cells decreased significantly with treatment. Loss of RhoA produced a reduction of Rholl, cyclin-b2, and beta-catenin messages showing that these genes are regulated downstream of RhoA. In contrast, runx-2 was not reduced. Inhibition of TGF beta 3 or TGF beta 2 activity caused a large reduction of RhoA message. These data place RhoA in TGF beta regulated pathways for both endothelial activation and mesenchymal invasion and demonstrate a functional requirement during EMT.