Research of extracellular matrix in the morphogenesis of tracnsposition of the great arteries

细胞外基质在大动脉转位形态发生中的研究

• 批准号: 07671281
• 负责人: YASUI Hiroshi
• 金额: $ 1.34万
• 依托单位: Tokyo Women's Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671281/
• 关键词: cardiac development; extracellular matrix; mouse; retinoic acid; integrin; インデグリン; 形態形成; 大血管転換症

First, we analized the morphogenetic process of the mouse model of transposition of the great arteries. We found that a pair of conus swellings, consisted of extracellular matrix, was hypoplastic and dysplatic before outflfow septum formation and that the outflow swellings lacked counterclockwise rotationand geve rise to straight outflow septum. Second, we looked at the localization of extracellular matrix along cardiac outflow tract destined to develop transposition and found that collagen type I,fibronectin and hyaluronaic acid distributed differently from the control. Then we looked at the immunohistochemical distribution of integrin alpha 4 which is a receptor of fibronectin. In the gestation day 10-12 mouse embryos, integrin alpha 4 was found at the endocardium-derived mesenchymes in the cardiac inflow and outflow tract, neural crest-derived outflow septeum, sinus venosus septum and left Cuvier's duct in accordance with the distribution of fibronectin, suggesting the active role role of integrin alpha 4 in the cardiac morphogenesis. However, integrin alpha 4 did not appear to be involved in the induction of hypoplasia of the cardiac jelly at gestation day 9. Receptors of collagen type I and/or hyaluronic acid might be associated with the process, however, this possibility is currently under investigation. On the other hand, by injecting retinoic acid two days earlier, complex heart defects associated with abnormality of leftright sidedness, i.e., viscero-atrial heteriraxy, are induced. Transposition of the great arteries appears among the heart defects. Less dose of rertinoic acid can induce the conotruncal anomalies with normal relation of the great arteries, which form a spectrum of vonotruncal anomalies includes transposition of great arteries. We plan to investigate the abnormality of ectracellular matrices, their receptors and their signal transduction pathways in those extended model of transposition.

首先，我们分析了大动脉转位小鼠模型的形态发生过程。我们发现一对由细胞外基质组成的圆锥体在流出隔形成前发育不良，流出隔缺乏逆时针旋转，并上升为直的流出隔。其次，我们观察了细胞外基质沿着心脏流出道的定位，发现I型胶原、纤连蛋白和透明质酸的分布与对照组不同。然后我们观察了纤维连接蛋白受体整合素α 4的免疫组织化学分布。在孕10 - 12天的小鼠胚胎中，整合素α 4在心脏流入道和流出道、神经嵴流出隔、静脉窦隔和左居维叶管的心内膜间充质中均有表达，与纤维连接蛋白的分布一致，提示整合素α 4在心脏形态发生中的积极作用。然而，整合素α 4似乎并没有参与诱导发育不全的心胶在妊娠第9天。I型胶原蛋白和/或透明质酸的受体可能与该过程相关，然而，这种可能性目前正在调查中。另一方面，通过两天前注射维甲酸，与左侧偏左异常相关的复杂心脏缺陷，即，内脏-心房的不对称性。大动脉转位是心脏畸形中的一种。小剂量的维甲酸可诱发大动脉正常关系的圆锥动脉干异常，形成包括大动脉转位在内的圆锥动脉干异常谱。我们计划在这些扩展的转座模型中研究细胞外基质的异常及其受体和信号转导通路。