权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular Mechanisms of Tissue Regeneration through the Conversion of HGF Receptor Signaling in Response of Injury

通过损伤反应中 HGF 受体信号转导实现组织再生的分子机制

基本信息

批准号：
18390087
负责人：
NAKAMURA Toshikazu
金额：
$ 8.57万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
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-18390087/
关键词：
HGF c-Met Growth Regulation Signal Transduction Tissue Regeneration Phosohatase Tissue Iniury Knockout Mouse Met 細胞増殖制御分子機構高密度培養

项目摘要

(1) Regulation of HGF/c-Met activation through tyrosine dephosphrylation by LAR:Inhibition of cell proliferation regulated by cell-cell contact is a fundamental characteristic of normal cells. In hepatocytes cultured at a confluent cell density, HGF stimulation induced transient c-Met tyrosine phosphorylation and failed to induce mitogenic response. We found that LAR plays a definitive role in inactivation, i.e. tyrosine dephosphorylation of c-Met through their physical interaction, which specifically occurs in hepatocytes under confluent condition. We published these results in J-Biol-Chem 281 : 8765 (2006).(2) Physiological significance of HGF/c-Met activation in cholestatic injury:We used a surgical technique of bile duct ligation (BDL) to induce cholestatic conditions in mice. After the BDL surgery, HGF and c-Met mRNA levels transiently increased in livers. Furthmore, we obtained evidence that endogenous HGF is involved in the physiological protection of hepatocyte cell death including necrosis and apoptosis. We published these results in Am-J-Physiol 292 : G639 (2007).(3) Generation of knock-in mice expressing only mutated c-Met (ΔJxt-Met):The phosphorylation status of juxtamembrane Ser-985 of c-Met plays functional regulatory role in activation of c-Met. c-Met has a splice variant that lacks a cytoplasmic juxtamembrane region (ΔJxt-Met). To analyze the function of ΔJxt-Met, we generated knock-in mice expressing only ΔJxt form of c-Met. Homozygous mutant mice died during neonatal period. Pathological analysis is now in progress.

(1)LAR通过酪氨酸去磷酸化调节HGF/c-Met活化：通过细胞-细胞接触调节的细胞增殖抑制是正常细胞的基本特征。在以汇合细胞密度培养的肝细胞中，HGF刺激诱导瞬时c-Met酪氨酸磷酸化，但未能诱导促有丝分裂反应。我们发现LAR在失活中起决定性作用，即通过它们的物理相互作用使c-Met的酪氨酸去磷酸化，这特别发生在汇合条件下的肝细胞中。我们将这些结果发表在J-Biol-Chem 281：8765（2006）中。(2)HGF/c-Met激活在胆汁淤积性损伤中的生理学意义：我们使用胆管结扎（BDL）的手术技术在小鼠中诱导胆汁淤积状况。BDL手术后，肝脏中HGF和c-Met mRNA水平短暂升高。此外，我们还获得了证据表明，内源性HGF参与了肝细胞死亡的生理保护，包括坏死和凋亡。我们在Am-J-Physiol 292：G639（2007）中发表了这些结果。(3)仅表达突变c-Met（ΔJxt-Met）的敲入小鼠的产生：c-Met的胞膜Ser-985磷酸化状态在c-Met的活化中起功能性调节作用。c-Met有一个剪接变体，缺少胞质质膜区（ΔJxt-Met）。为了分析ΔJxt-Met的功能，我们产生了仅表达ΔJxt形式的c-Met的敲入小鼠。纯合子突变小鼠在新生期死亡。病理分析正在进行中。

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）

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 lives cirrhosis (Review).

肝细胞生长因子：一种治疗急性肝炎和肝硬化的再生药物（综述）。

DOI：
发表时间：
2007
期刊：
Regenerative Med. (In press)
影响因子：
0
作者：
Yin;J.;Sakamoto;K.;Zhang;H.;Ito;Z.;Imagama;S.;Kishida;S.;Natori;T.;Sawada;M.;Matsuyama;Y.;Kadomatsu;K.;Ooya W.et al.;Hideki Sumimoto;Mizuno S. et al.
通讯作者：
Mizuno S. et al.

NK4 suppresses CT26 lung metastasis by inhibiting adhesion of tumor cells to endothelial cells

NK4通过抑制肿瘤细胞与内皮细胞的粘附来抑制CT26肺转移