León Y, Sanz C, Giráldez F, Varela-Nieto I
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
J Comp Neurol. 1998 Aug 31;398(3):323-32. doi: 10.1002/(sici)1096-9861(19980831)398:3<323::aid-cne2>3.0.co;2-1.
The present report investigates the cellular mechanisms involved in the regulation of cell proliferation by insulin and insulin-like growth factor-I (IGF-I) in the developing inner ear. The results show that insulin and IGF-I stimulate cell proliferation in the otic vesicle. This effect is associated with the induction of the expression of the nuclear proto-oncogene c-jun. The temporal profile of Jun expression coincided with the proliferative period of growth of the otic vesicle. IGF-I promoted the hydrolysis of a membrane glycosyl-phosphatidylinositol, which was characterised as the endogenous precursor for inositol phosphoglycan (IPG). Both purified IPG and a synthetic analogue, 6-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-D-myoinositol-1,2-cyclic phosphate (C3), were able to mimic the effects of IGF-I on Jun expression. Anti-IPG antibodies blocked the effects of IGF-I, which were rescued by the addition of IPG or its analogue. These results suggest that the sequence involving the hydrolysis of membrane glycolipids and the expression of c-jun and c-fos proto-oncogenes is part of the mechanism that activates cell division in response to insulin and IGF-I during early organogenesis of the avian inner ear. The implications of these observations for otic development and regeneration are briefly discussed.
本报告研究了发育中的内耳中胰岛素和胰岛素样生长因子-I（IGF-I）调节细胞增殖所涉及的细胞机制。结果表明，胰岛素和IGF-I刺激耳泡中的细胞增殖。这种作用与核原癌基因c-jun表达的诱导有关。Jun表达的时间模式与耳泡生长的增殖期一致。IGF-I促进了一种膜糖基磷脂酰肌醇的水解，其特征为肌醇磷酸聚糖（IPG）的内源性前体。纯化的IPG和一种合成类似物6-O-(2-氨基-2-脱氧-α-D-吡喃葡萄糖基)-D-肌醇-1,2-环磷酸酯（C3）均能够模拟IGF-I对Jun表达的影响。抗IPG抗体阻断了IGF-I的作用，而添加IPG或其类似物可挽救这种作用。这些结果表明，涉及膜糖脂水解以及c-jun和c-fos原癌基因表达的序列是在鸟类内耳早期器官发生过程中响应胰岛素和IGF-I激活细胞分裂机制的一部分。简要讨论了这些观察结果对耳发育和再生的意义。
