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

蛋白酪氨酸激酶（PTKs）的激活被认为与细胞分化和增殖有关。为了阐明酪氨酸激酶基因在肥大心脏中的作用，我们分析了受体型PTKs在大鼠正常和2肾i夹和doca盐高血压肥大心脏中的表达模式。RT-PCR使用退化引物进行，这些引物是从受体型PTKs的催化结构域中高度保守的区域设计的。比较这些PTK mrna在正常和肥大心脏中的表达水平。我们进行了半竞争性RT-PCR和免疫组织化学分析。对81个PTKs克隆的核苷酸测序显示，在大鼠心脏中有10个受体类型，5个非受体类型和2个未知类型。Tie-2/Tek、Ryk、IGF-I受体作为受体型PTKs的成员在大鼠心脏中大量表达。免疫组织化学和RT-PCR显示pdgf - α的存在。受体，pdgf受体和。正常和肥大心脏中的FGF-3受体。我们还通过免疫组织化学和RT-PCR证实了心脏中存在Fit-1、KDR/Flk-1及其配体VEGF、c-Met及其配体HGF、Tie-1、Tie-2/Tek。心肌HGF和c-Met在肥厚的大鼠，特别是2肾i夹大鼠中表达较强。这些发现表明，HGF/c-Met相互作用可能不仅在血管生成中起重要作用，而且在心脏肥大和重构中也起重要作用。

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.