Study on the adaptive plasticity of mechanical components of the vascular wall

作为一种新的血管新生模型，我们研究了Thy-1肾炎在大鼠体内的恢复阶段。静脉注射表达于系膜细胞膜表面的Thy-1.1分子单克隆抗体后，在补体的帮助下破坏大鼠肾系膜细胞，导致肾小球毛细血管增宽并结。肾小球毛细血管在注射抗体后一个月内恢复。我们通过扫描显微镜观察血管铸型的恢复过程，发现一种肠套式的毛细血管生长，其中原有的毛细血管通过毛细血管壁延伸到毛细血管腔而分裂成两部分。血管紧张素II是一种最强大的血管收缩物质，可引起血管平滑肌细胞的强烈收缩。我们分析了1a型抗紧张素受体零突变小鼠平滑肌细胞对缺乏抗紧张素II的反应。在小鼠的动脉壁中，血管平滑肌细胞在介质的管腔面和基面均形成较厚的血管壁，呈零星分布，取向异常。作为一种特殊类型血管壁的例子，我们重点讨论了肾小球滤过屏障，特别是足细胞。为了研究足细胞的性质，我们与新潟大学肾脏研究所联合开发了一种从大鼠肾小球中分离活足细胞的技术。我们对足细胞的细胞骨架进行了详细的研究，并在狭缝隔膜底部发现了两个分子（podocin和FAT）的分布，这对了解狭缝隔膜的分子结构有很大的帮助。我们还研究了plcatenin的分子动力学（与筑波大学病理学系合作）以及含有微管的足细胞主要过程的形成过程（与海德堡大学解剖研究所合作）。少

As a new model of vascular neogenesis, we studied recovery phase of Thy-1 nephritis in the rat. After intravenous injection of monoclonal antibody for Thy-1.1 molecule which is expressed on the membrane surface of mesangial cells, the mesangial cells of the rat kidney were destroyed with help of complement, resulting in widening and coalescence of glomerular capillaries. The glomerular capillaries are recovered within a months after injection of the antibody. We observed the process of recovery by means of scanning microscopic observation of the vascular cast, and found an intussusceptive type of capillary growth in which the preexisting capillaries are splitted into two by extension of the capillary wall into the capillary lumina.Angiotensin II is a most powerful vascoconstrictic substance and cause strong contraction of vascular smooth muscle cells. We analyzed the response of smooth muscles cells to absence of aniotensin II in null mutant mice of type 1a recptor for antiotensin II. … More In the arterial wall of the mice, the vascular smooth muscle cells constructs thicker wall with sporadic population with abnormal orientation both on the luminal and basal surface of the media.As an example of special type of vascular wall, we focused on the glomerular filtration barrier especially on the podocytes. In order to study the nature of the podocytes, we newly developed a technique to isolate living podocytes from the rat glomeruli (joint work with Kidney Research Institute, Niigata University). We studied the cytoskeleton of the podocytes in detail and discovered distribution of two molecules (podocin and FAT) at the base of slit diaphragm, discovery which contribute much to understanding of molecular architecture of slit diaphragm. We studied also molecular dynamics of pl catenin (joint work with Department of Pathology, Tsukuba University) as well as forming process of major processes of podocytes containing microtubules (joint work with Institute of Anatomy, Heidelberg University). Less