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Roles of interstitial cells on the recovery process from acute renal failure

间质细胞在急性肾衰竭恢复过程中的作用

基本信息

批准号：
13671107
负责人：
FUJIGAKI Yoshihide
金额：
$ 2.3万
依托单位：
Hamamatsu University, School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

1. We reported that in uranyl acetate (UA)-induced acute renal failure (ARF) in rats, transient infiltration of macrophages and α-smooth muscle actin-positive myofibroblasts in the interstitium occurred in associalion with the peak activity of tubular regeneration after acute tubular injury and that the regeneration of tubular epithelial cells was inhibited by the suppression of the interstitial cellular response by mycophenolate mofetil. Based on the findings we concluded that myofibroblasts and infiltrating macrophages may contribute as in the wound healing process to cellular recovery in this ARF model.2. Mechanical tension judged by tubular dilatation may contribute to induce α-smooth muscle actin phenotype in association with stress fiber formation and intercellular junctions in fibroblastic cells to adjust tensional homeostasis and not to collapse the damaged nephron structures. Myofibroblasts may furnish cellular fibronectin to condition an environment for tubular proliferation. … More Fibronectin may be the scaffold for tissue formation and growth, initiate intercellular signaling events through binding to cell receptor (integrins). Moreover, myofibroblasts can provide growth factors in autocrine and/or paracrine fashion.3. Macrophages can produce several types of cytokines and growth factors, which promote epithelial cell proliferation. Macrophages may also function as scavengers and phagocytose cellular debris in the tubular lumen, cleaning the wound site to promote healing. Macrophaes that accumulated in the vicinity of the tubular basement membrane might act as outpost of the defense system to monitor incoming antigens.4. Although renal interstitial myofibroblasts and macrophages have often been regarded rather harmful in clinical and experimental settings as they are considered as indicators of interstitial fibrosis, the roles of myofibroblasts and macrophages in this ARF seemed to be all necessary components of wound healing. Further analysis of transient response of these interstitial cellular factors would be useful to explore the mechanisms of kidney repair and fibrosis. Less

1.在醋酸铀酰（UA）诱导的大鼠急性肾功能衰竭（ARF）中，肾小管内巨噬细胞和α-平滑肌肌动蛋白阳性肌成纤维细胞的浸润与急性肾小管损伤后肾小管再生的高峰活动有关，而霉酚酸酯抑制间质细胞反应可抑制肾小管上皮细胞的再生。基于这些发现，我们得出结论，在ARF模型中，肌成纤维细胞和浸润的巨噬细胞可能有助于伤口愈合过程中的细胞恢复。通过肾小管扩张判断的机械张力可能有助于诱导与成纤维细胞中的应力纤维形成和细胞间连接相关的α-平滑肌肌动蛋白表型，以调节张力稳态，而不是使受损的肾单位结构塌陷。肌成纤维细胞可以提供细胞纤连蛋白以调节肾小管增殖的环境。 ...更多信息纤维连接蛋白可能是组织形成和生长的支架，通过与细胞受体（整合素）结合启动细胞间信号传导。此外，肌成纤维细胞可以自分泌和/或旁分泌方式提供生长因子.巨噬细胞可以产生几种类型的细胞因子和生长因子，促进上皮细胞增殖。巨噬细胞还可以充当清道夫并吞噬管腔中的细胞碎片，清洁伤口部位以促进愈合。聚集在肾小管基底膜附近的巨噬细胞可能作为防御系统的前哨，监测传入的抗原.虽然肾间质肌成纤维细胞和巨噬细胞在临床和实验环境中通常被认为是相当有害的，因为它们被认为是间质纤维化的指标，但肌成纤维细胞和巨噬细胞在这种ARF中的作用似乎是伤口愈合的所有必要组成部分。进一步分析这些间质细胞因子的瞬时反应将有助于探讨肾脏修复和纤维化的机制。少