视黄酸途径和TGF-β3/Smad通路在胎鼠腭裂发生中的相互作用

项目名称： 视黄酸途径和TGF-β3/Smad通路在胎鼠腭裂发生中的相互作用

项目编号： No.U1204804

项目类型： 联合基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 李宁

作者单位： 河南农业大学

项目金额： 30万元

中文摘要： 视黄酸是VitA的生理活性形式，孕期VitA缺乏/过量可导致胚胎发育畸形。前期工作表明：视黄酸过量/缺乏可改变胎鼠腭组织中TGFβ及下游基因Smads的表达模式，并致仔代出现腭裂；另一方面，激活/阻断TGFβ受体，可抑制/上调VitA合成酶RALDH2 mRNA表达水平。我们据此提出假设：在腭发育过程中，视黄酸途径和TGFβ/Smad存在相互作用，二者协调关系的失衡是腭裂发生的机制之一。目前尚不清楚二者的协调模式及相互作用的分子机制。为此，在本立项中，我们拟借助现代组织学技术和分子生物学手段，在次腭发育后期，阐明：①视黄酸途径和TGFβ/Smad在时、空、量方面的协调模式；②二者相互作用对上皮组织降解、双侧腭板融合、及间充质组织增殖、分泌和分化等的调节作用；③二者协调失衡致腭裂发生的始发环节及关键信息分子；到达从不同层面和角度揭示相关化合物诱发腭裂的作用机制，为围产期保健提供实验依据。

中文关键词： 视黄酸；TGFβ/Smad；相互作用；腭裂；

英文摘要： Retinoic acid (RA) is the most potent active metabolite of vitamin A. Maternal vitamin A deficiency or excess leads to fetal developmental malformations. Our previous results demonstrated that RA deficiency or excess gave rise to cleft palate of filial mice through perturbation of TGFβ/Smad signaling during embryonic palatogenesis; moreover, activation/inactivation of TGFβ receptor decreased/increased the mRNA expression of retinaldehyde dehydrogenase (RALDH2), which is an anabolic enzyme of RA. This suggests that the balance of these two pathways may play fundamental roles during development of multicellular organisms. We herein hypothesized that RA signaling can functionally interact with the TGFβ/Smad pathway during the palatal development, and the unbalance between these two pathways may be one of the major underlying molecular mechanisms for the induction of cleft palate. However, the models of cross-talk, the underlying molecular mechanisms and the molecular pathological features for the interaction between these two pathway have remained unclear. In this project, we aim to explore these scientific questions as below during second palate development by use of modern histologic technology and molecular biological techniques: ① in the aspects of of RA and TGFβ/Smad with spatial-, temporal- and quantitative-

英文关键词： Retinoic Acid；TGFβ/Smad；interaction；cleft palate；