Molecular Biology Research Laboratory, Department of Otorhinolaryngology, Institute of Cell- and Neurobiology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Charitéplatz 1, Germany.
Hear Res. 2010 Mar;261(1-2):9-21. doi: 10.1016/j.heares.2009.12.017. Epub 2009 Dec 16.
Based on observations that mutations of GATA-3 are responsible for the HDR-syndrome (hypoparathyroidism, deafness, renal defects) and that GATA-transcription factors have an important role to play in inner ear development, we hypothesized that these transcription factors may be involved in regulatory changes of prestin transcription. To prove this, we examined in parallel the expression of mRNA of prestin and Gata-3,-2 and Gata-1 in the organ of Corti during early postnatal development of rats and in organotypic cultures. Remarkable relations are observed between prestin and Gata-3,-2 expression in organ of Corti preparations in vivo and in vitro: (i) Gata-3,-2 expression display similar apical-basal gradients as prestin mRNA levels. (ii) The prestin expression increases between postnatal day two and postnatal day eight by a factor of about four in the apical and middle segments and by a factor of two in the basal part. Highly significant Pearson correlation coefficients were observed between Gata-3,-2 mRNA and prestin levels when the data were evaluated by regression analyses. (iii) Parallel changes of prestin mRNA and Gata-3,-2 mRNA levels were observed in response to thyroid hormone and to gemfibrozil application. These observations suggest a regulatory role played by the Gata-3,-2 transcription factors in prestin expression.
基于 GATA-3 突变负责 HDR 综合征(甲状旁腺功能减退、耳聋、肾脏缺陷)的观察结果,以及 GATA 转录因子在内耳发育中具有重要作用的假设,我们假设这些转录因子可能参与 prestin 转录的调节变化。为了证明这一点,我们平行研究了大鼠出生后早期发育过程中耳蜗器官中和体外培养物中 prestin 和 Gata-3、-2 和 Gata-1 的 mRNA 表达。在体内和体外的耳蜗器官制备物中,观察到 prestin 和 Gata-3、-2 表达之间存在显著的关系:(i)Gata-3、-2 的表达呈现出与 prestin mRNA 水平相似的顶底梯度。(ii)在出生后第 2 天到第 8 天,顶段和中段的 prestin 表达增加了约 4 倍,基底段增加了 2 倍。当通过回归分析评估数据时,观察到 Gata-3、-2 mRNA 和 prestin 水平之间存在高度显著的皮尔逊相关系数。(iii)观察到 prestin mRNA 和 Gata-3、-2 mRNA 水平的平行变化,对甲状腺激素和 gemfibrozil 的应用有反应。这些观察结果表明 Gata-3、-2 转录因子在 prestin 表达中发挥调节作用。