Rapamycin suppresses hypoxia/reoxygenation-induced islet injury by up-regulation of miR-21 via PI3K/Akt signalling pathway
Rapamycin suppresses hypoxia/reoxygenation-induced islet injury by up-regulation of miR-21 via PI3K/Akt signalling pathway
复制标题
雷帕霉素通过 PI3K/Akt 信号通路上调 miR-21 抑制缺氧/复氧诱导的胰岛损伤
DOI：
10.1111/cpr.12306
复制
发表时间：
2017-02-01
影响因子：
8.5
通讯作者：
Xu, Shuyun
中科院分区：
文献类型：
--
作者：
Zhang, Yi;He, Sirong;Xu, Shuyun
目的：越来越多的证据表明microRNA在缺氧/复氧（H/R）损伤的调控中起重要作用，其表达与mTORC活性相关，我们认为雷帕霉素通过调控microRNA的表达来调节H/R诱导的胰岛损伤。材料和方法：我们研究了雷帕霉素处理是否可以改变胰岛中miRNA的表达谱。此外，我们还评估了H/R或同基因胰岛移植后胰岛细胞凋亡和功能。我们发现，雷帕霉素处理显著减少H/R诱导的胰岛细胞凋亡，并在体内和体外改善胰岛功能，并且miR-21基因转录受雷帕霉素控制。雷帕霉素对miR-21表达的上调作用在体外被抑制。此外，我们的研究清楚地表明，miR-21是必不可少的雷帕霉素介导的保护胰岛免受H/R injury.Discussion：我们的研究结果表明，上调miR-21在胰岛中的功能与雷帕霉素治疗或过表达的miR-21可能代表了一个潜在的新的治疗H/R injury.Conclusion：本研究的结果清楚地表明，雷帕霉素通过PI 3 K/Akt诱导miR-21表达来对胰岛H/R损伤发挥抑制作用。
Objectives: Increasing evidences indicate that microRNAs may play a critical role in the regulation of hypoxia/ reoxygenation (H/R) injury, and their expression is associated with mTORC activity.We propose that rapamycin modulates H/R-induced islets injury by regulating microRNA expression. Materials and methods: We investigated whether rapamycin treatment could alter the expression profile of miRNAs in islets. Furthermore, we assessed the islet apoptosis and function after H/R or syngeneic islet transplantation.Results: We found that rapamycin treatment significantly decreased H/R-induced islet apoptosis, and improved islet function in vivo and in vitro, and that miR-21 gene transcription is controlled by rapamycin.When the PI3k/Akt signalling pathways was blocked by wortmannin, the up-regulative effects of rapamycin on miR-21 expression were inhibited in vitro. Furthermore, our study clearly demonstrates that miR-21 is essential for the rapamycin-mediated protection islets against H/R injury.Discussion: Our findings indicate that up-regulation of miR-21 function in islets by treatment with rapamycin or overexpression of the miR-21 could represent a potential new therapy for the treatment of H/R injury.Conclusion: The results of this study clearly suggest that rapamycin exerts its inhibitory effects on islets H/R injury by inducing miR-21 expression via PI3K/Akt.