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Identification of tubular epithelial stem cells and their roles on recovery from acute renal failure

肾小管上皮干细胞的鉴定及其在急性肾衰竭恢复中的作用

基本信息

批准号：
15590848
负责人：
FUJIGAKI Yoshihide
金额：
$ 2.24万
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：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590848/
关键词：
epithelial stem cell proximal tubular cell acute renal failure uranyl acetate autoradiography bromodeoxyuridin 5-fluorouracil megalin bromodeoxyuridin 近位尿細管上皮 Ki67 cyclin B1

项目摘要

Initially regenerating cells in uranyl acetae-induced acute renal failure was investigated in relation to the epithelial stem cells. The findings are as follows.1)Initially regenerating cells regardless of degrees of injury in S3 segment by different doses of uranyl acetate injection are dedifferentiated pre-existing mature proximal tubular cells, which may be responsible for focal repair of S3.2)Initially regenerating cells showed 3H-thymidine label-retaining, and cells in the distal S3 even after contributing to renewal of the entire S3 were identified as label retaining cells for about 6 weeks.3)Initially regenerating cells in the distal S3 showed a large capacity for proliferation and ability to produce daughter cells capable for the repair of entire S3.4)Daughter (proliferating) cells of initially regenerating cells may die from 5-fluorouracil (FU) treatment, while initially regenerating cells in the distal S3 were 5-FU resistant and confined there. After stopping 5-FU, those cells proliferated toward the proximal direction of S3 with showing mature proximal tubular phenotype.The findings indicate that initially regenerating PT cells in the distal S3 show slow cycling under steady condition, a large capacity for proliferation. ability to produce daughter cells capable for the repair of entire S3. and 5-FU resistant, suggesting that some PT cells in the distal S3 might be a stem/progenitor cell population in S3 segment of proximal tubule. In addition, the cells may exist in a location between S3 and the thin descending limb of Henle, where might be stern cell niche. Further analysis of the cells in the distal S3 in relation to epithelial stem cells would contribute to development of new therapeutic strategy for acute renal failure.

最初，研究了乙酸铀酰诱导的急性肾功能衰竭中再生细胞与上皮干细胞的关系。结果如下：1)无论注射不同剂量的醋酸铀酰对S3节段的损伤程度如何，最初再生的细胞都是去分化的成熟近端小管细胞，这可能是S3节段局部修复的原因。3)最初再生的细胞显示~3H-胸腺嘧啶核苷标记保留，3)S3远端的初始再生细胞表现出很大的增殖能力和产生能够修复整个S3的子代细胞的能力。3)最初再生细胞的子代(增殖)细胞可能会因5-氟尿嘧啶(5-FU)处理而死亡，而最初在S3远端再生的细胞是5-FU耐药的并被限制在那里。停止5-FU后，这些细胞向S3近端方向增殖，并呈现成熟的近端小管表型。结果表明，S3远端再生的PT细胞在稳定条件下表现出缓慢的周期，增殖能力较大。能够产生能够修复整个S3的子代细胞。5-FU耐药，提示S3远端部分PT细胞可能是近端小管S3段的干/祖细胞群。此外，细胞可能存在于S3和Henle细小降支之间的位置，在那里可能是尾细胞壁龛。进一步分析S3远端细胞与上皮干细胞的关系将有助于开发治疗急性肾功能衰竭的新策略。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The induction of cell cycle regulatory and DNA repair proteins in cisplatin-induced acute renal failure

DOI：
10.1016/j.taap.2004.04.003
发表时间：
2004-10-15
期刊：
TOXICOLOGY AND APPLIED PHARMACOLOGY
影响因子：
3.8
作者：
Zhou, H;Kato, A;Hishida, A
通讯作者：
Hishida, A

Ultrastructure of tubular epithelial cells in response to microembolism-induced chronic ischemic injury in rats

DOI：
10.1159/000074841
发表时间：
2003-01-01
期刊：
NEPHRON EXPERIMENTAL NEPHROLOGY
影响因子：
0
作者：
Fujigaki, Y;Kimura, M;Hishida, A
通讯作者：
Hishida, A

Transient myofibroblast differentiation of interstitial fibroblastic cells relevant to tubular dilatation in uranyl acetate-induced acute renal failure in rats

DOI：
10.1007/s00428-004-1155-5
发表时间：
2005-02-01
期刊：
VIRCHOWS ARCHIV
影响因子：
3.5
作者：
Fujigaki, Y;Muranaka, Y;Hishida, A
通讯作者：
Hishida, A

Ultrastructure of tubular epithelial cells in responce to microembolism-induced chronic ischemic injury in rats

肾小管上皮细胞超微结构对微栓塞诱导的大鼠慢性缺血性损伤的响应

DOI：
发表时间：
2003
期刊：
Nephron Exp Nephrol 94・4
影响因子：
0
作者：
Noguchi M;Itoh K;Suekane S;Yao A;Suetsugu N;Katagiri K;Yamada A;Yamana H;Noda S.;Hua Zhou;Haruo Hanawa;Yoshihide Fujigaki
通讯作者：
Yoshihide Fujigaki

Plasma protein extravasation and vascular endothelial growth factor expression with endothelial nitric oxide synthase induction in gentamicin-induced acute renal failure in rats.

庆大霉素诱导的大鼠急性肾衰竭中内皮一氧化氮合酶诱导的血浆蛋白外渗和血管内皮生长因子表达。