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Molecular basis for renal regeneration : New approach using a nephron-specific HGF-knockout mice

肾再生的分子基础：使用肾单位特异性 HGF 敲除小鼠的新方法

基本信息

批准号：
18590369
负责人：
MIZUNO Shinya
金额：
$ 2.02万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590369/
关键词：
HGF c-Met Nephron Renal regeneration Renal diseases Molecular mechanism Renal protection Knockout mice Met 組織修復腎保護効果

项目摘要

It was suggested that HGF may be a key physiological regulator for tissue reconstruction after acute renal injuries, but there was little direct evidence for supporting this hypothesis. Herein we provide evidence to show that endohenous HGF/c-Met axis plays an important role for inducing renal regeneration in mice after acute renal injury, using anti-HGF antibody or HGF gene targeting techniques, as follows :(1) Renal tubular proliferation became evident in mice at 48-hr after renal ischemia and reperfusion. When anti-HGF IgG was administered into mice, tubular regeneration was inhibited, associated with the enhancement of bone marrow engraftment. These findings indicated the importace of endogenous HGF to elicit tubular cell proliferation, rather than stem cell involvement under renal ischemia.(2) Is is known that 70%-partial hepatectomy attenuated the onset of acute renal failure after muscular damages in rats. Anti-HGF IgG diminished the protection of renal injury by 70%-hepatectomy, hence indicating the pivotal roles of endogenous HGF, induced by the loss in hepatic lobes, for protection of renal damage after crush syndorome.(3) We prepared the podocyte-specific deletion of HGF gene, using a Cre-LoxP system. There was no significant lesions in the renal tissues of the HGF-deficient mice during a developmental stage. However, HGF-deficient mice seemed to be more sensitive to a chemical drug, which causes proteinuria.

有人认为，肝细胞生长因子可能是急性肾损伤后组织重建的关键生理调节因子，但几乎没有直接证据支持这一假设。本研究利用抗HGF抗体或HGF基因打靶技术，证实了内源性HGF/c-Met轴在急性肾损伤后诱导小鼠肾脏再生中的重要作用，具体表现为：（1）肾缺血再灌注48小时，肾小管增生明显。当给予小鼠抗HGF IgG时，肾小管再生受到抑制，与骨髓植入的增强相关。这些发现表明，在肾缺血时，内源性HGF引起肾小管细胞增殖的重要性，而不是干细胞参与。(2)已知70%肝部分切除减轻了大鼠肌肉损伤后急性肾衰竭的发作。抗HGF IgG减弱了70%肝切除术对肾损伤的保护作用，因此表明由肝叶损失诱导的内源性HGF在挤压综合征后保护肾损伤中的关键作用。(3)我们利用Cre-LoxP系统制备了足细胞特异性的HGF基因缺失。在发育阶段，HGF缺陷小鼠的肾组织中没有明显的病变。然而，缺乏HGF的小鼠似乎对一种化学药物更敏感，这会导致蛋白尿。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Gene therapy

DOI：
10.1016/b978-0-12-818422-6.00029-0
发表时间：
2020
期刊：
Principles of Tissue Engineering
影响因子：
0
作者：
S. Worgall;R. Crystal
通讯作者：
S. Worgall;R. Crystal

Hepatocyte growth factor attenuates cerebral ischemia-induced increase in permeability of blood-brain barrier and decreases in expression of tight junctional proteins in cerebral vessels.

肝细胞生长因子可减弱脑缺血引起的血脑屏障通透性增加和脑血管中紧密连接蛋白表达的减少。

DOI：
发表时间：
2006
期刊：
Neurosci Lett. 407
影响因子：
0
作者：
Date;I.;Takagi;N.;Takagi;K.;Tanonaka;K.;Funakoshi;H.;Matsumoto;K.;Nakamura;T.;akeo;S;Machide M. et al.;Sumi T.et al.;Matsumoto K. et al.;Namiki Y. et al.;Hosseinkhani H. et al.;Azuma J. et al.;Ogura Y. et al.;Tada T.et al.;Ono K.et al.;Niimura M. et al.;Date I.et al.
通讯作者：
Date I.et al.

Hepatocyte growth factor : A regenerative drug for acute hepatitis and liver cirrhosis (Review).

肝细胞生长因子：治疗急性肝炎和肝硬化的再生药物（综述）。