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

作为一种新的血管新生模型，我们研究了大鼠Thy-1肾炎的恢复期。静脉注射表达于系膜细胞膜表面的Thy-1.1分子的单克隆抗体后，大鼠肾小球系膜细胞在补体的帮助下被破坏，导致肾小球毛细血管增宽和合并。肾小球毛细血管在注射抗体后一个月内恢复。我们用扫描显微镜观察血管铸型的恢复过程，发现毛细血管生长为内陷型，即原有毛细血管壁向毛细血管腔内延伸，使毛细血管一分为二。血管紧张素Ⅱ是一种强有力的缩血管物质，能引起血管平滑肌细胞的强烈收缩。我们分析了平滑肌细胞对缺乏抗血管紧张素II的1a型受体无效突变小鼠的反应。 关于我们 在小鼠动脉壁中，血管平滑肌细胞在中膜的腔面和基底面上构成较厚的管壁，并具有散在的异常取向的细胞群，作为特殊类型血管壁的一个例子，我们重点研究了肾小球滤过屏障，特别是足细胞。为了研究足细胞的性质，我们新开发了一种从大鼠肾小球中分离活足细胞的技术（与新泻大学肾脏研究所的合作）。我们对足细胞的细胞骨架进行了详细的研究，发现了两种分子（podocin和FAT）在狭缝隔膜底部的分布，这一发现有助于理解狭缝隔膜的分子结构。我们还研究了β-连环蛋白的分子动力学（与筑波大学病理学系合作）以及含有微管的足细胞的主要过程的形成过程（与海德堡大学解剖学研究所合作）。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