Involvement of receptor-type tyrosine kinase gene families in cardiac hypertrophy.

受体型酪氨酸激酶基因家族参与心脏肥大。

• 批准号: 09670729
• 负责人: SETO Shinji
• 金额: $ 1.98万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670729/
• 关键词: Receptor-type PTKs; Left ventricular hypertrophy; HGF; c-Met; VEGF; Flt-Flk; Angiopoietin; Tie-Tek; Tek; Flk-1,Flt-1

Activation of protein tyrosine kinases (PTKs) has been postulated to be involved in cell differentiation and proliferation. To elucidate the involvement of tyrosine kinase genes in hypertrophied heart, we analyzed the expression patterns of receptor-type PTKs in the normal and 2 kidney-I clip and DOCA-salt hypertensive hypertrophied heart in the rats. RT-PCR was performed using degenerated primers which were designed from highly conserved regions in the catalytic domains of receptor-type PTKs. To compare the expression level of these PTK mRNAs in the normal and hypertrophied heart, . we performed semi-competitive RT-PCR and immunohistochemical analysis. Nucleotide sequencing of 81 clones of PTKs revealed 10 receptor-type, 5 nonreceptor-type and 2 unknowns in the rat heart. Tie-2/Tek, Ryk, IGF-I receptor were abundantly expressed in the rat heart as a member of receptor-type PTKs. Immunohistochemistry and RT-PCR demonstrated the presence of PDGF-alpha. receptor, PDGF-beta receptor and .FGF-3 receptor in both normal and hypertrophied hearts. We also confirmed the Fit-1, KDR/Flk-1, and their ligand VEGF, c-Met and its ligand HGF, and Tie-1, Tie-2/Tek in the hearts by immunohistochemistry and RT-PCR.The expression of cardiac HGF and c-Met in the hypertrophied hearts especially 2 kidney-I clip rats were strong in protein level. These findings suggest that HGF/c-Met interactions may play an important role not only in angiogenesis but also in cardiac hypertrophy and remodeling.

蛋白酪氨酸激酶(PTKs)的激活被认为与细胞的分化和增殖有关。为了阐明酪氨酸激酶基因在肥厚心脏中的作用，我们分析了正常大鼠、2只肾I夹和DOCA盐型高血压大鼠肥厚心脏中受体PTKs的表达模式。RT-PCR使用从受体类型的PTKs的催化区高度保守的区域设计的简并引物。为了比较这些PTK基因在正常心脏和肥厚心脏中的表达水平。进行半竞争性RT-PCR和免疫组织化学分析。对81个PTKs克隆的核苷酸序列分析表明，在大鼠心脏中有10个受体类型，5个非受体类型和2个未知。Tie-2/Tek、Ryk、IGF-I受体作为受体PTKs的一员，在大鼠心脏中大量表达。免疫组织化学和RT-PCR证实PDGF-α的表达。正常和肥厚心脏中的受体、PDGF-β受体和成纤维细胞生长因子-3受体。免疫组织化学和RT-PCR法证实FIT-1、KDR/Flk-1及其配体VEGF、c-Met及其配体HGF、Tie-1、Tie-2/Tek在心脏组织中有较强的表达。这些结果表明，HGF/c-Met相互作用不仅在血管生成中发挥重要作用，而且在心肌肥大和重塑过程中也发挥重要作用。