Department of Bioscience, Fukui Prefectural University, Fukui, Japan.
School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan.
Adv Exp Med Biol. 2017;975 Pt 1:497-502. doi: 10.1007/978-94-024-1079-2_39.
Tissue taurine depletion mediated by knocking out the taurine transporter causes several skeletal muscle abnormalities, including acceleration of cellular aging. In the present study, we investigated the signaling pathway involved in the acceleration of skeletal muscle aging by tissue taurine depletion using the bioinformatic approach of transcriptome data. We previously performed transcriptome analysis on skeletal muscle of taurine transporter knockout (TauTKO) mice using DNA microarray. Bioinformatic analysis of transcriptome data predicted the activation of SMAD3 and β-catenin as upstream signaling molecules of cyclin-dependent kinase inhibitor 2A (CDKN2A, also called p16INK4A), which is a biomarker gene of cellular senescence. The activation of SMAD3 and β-catenin in old TauTKO muscle was verified by western blot analysis. These data indicate that SMAD3- and β-catenin-dependent induction occurs in the TauTKO mouse.
通过敲除牛磺酸转运蛋白导致的组织牛磺酸耗竭会引起几种骨骼肌异常，包括细胞衰老加速。在本研究中，我们使用转录组数据的生物信息学方法研究了组织牛磺酸耗竭引起的骨骼肌衰老加速的信号通路。我们之前使用 DNA 微阵列对牛磺酸转运蛋白敲除（TauTKO）小鼠的骨骼肌进行了转录组分析。转录组数据的生物信息学分析预测 SMAD3 和 β-catenin 的激活是细胞周期蛋白依赖性激酶抑制剂 2A（CDKN2A，也称为 p16INK4A）的上游信号分子，CDKN2A 是细胞衰老的生物标志物基因。通过 Western blot 分析验证了衰老的 TauTKO 肌肉中 SMAD3 和 β-catenin 的激活。这些数据表明，SMAD3 和 β-catenin 依赖性诱导发生在 TauTKO 小鼠中。
