Elucidation of physiological function and mechanism of DA-Raf in cardiac hypertrophy and heart failure

我们已经鉴定出DA-Raf（删除了A-Raf），它是由Araf基因选择性剪接产生的。它包含 Ras 结合结构域，但缺乏激酶结构域。为了阐明 DA-Raf 的生理功能及其机制，我们培育了 DAraf 基因缺陷（KO）小鼠，其中 Araf 表达不受影响。由于KO小鼠缺乏肌成纤维细胞，肺泡发育不良。另一方面，高水平表达 DA-Raf 的肺泡上皮 2 型细胞 (AEC2) 可能通过上皮间质转化转化为肌成纤维细胞。这些结果表明 DA-Raf 通过调节 AEC2-肌成纤维细胞转变中的 Ras-ERK 通路在肺泡化中发挥重要作用。

We have identified DA-Raf (deleted A-Raf), which is generated by alternative splicing from Araf gene. It contains the Ras-binding domain, but lacks the kinase domain. To elucidate physiological functions of DA-Raf and their mechanisms, we generated DAraf gene-deficient (KO) mice, in which Araf expression is not affected. Lung alveoli were poorly developed due to the lack of myofibroblasts in the KO mice. On the other hand, alveolar epithelial type 2 cells (AEC2), which expressed DA-Raf at high level, might transform by epithelial-mesenchymal transition to myofibroblasts. These results imply that DA-Raf plays essential roles in alveolarization by regulating the Ras-ERK pathway in AEC2-myofibrblast transition.