Yi Zhang1, Sirong He2, Xiaojion Du1, Yaowen Jiang3, Bole Tian1, Shuyun Xu3. 1. Department of Hepatobiliopancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China. 2. Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, China. 3. Department of Emergency, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Abstract
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.
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.
Authors: F Serr; H Lauer; B Armann; S Ludwig; J Thiery; M Fiedler; U Ceglarek; A Tannapfel; D Uhlmann; J Hauss; H Witzigmann Journal: Am J Transplant Date: 2007-01 Impact factor: 8.086
Authors: Jonathan G Godwin; Xupeng Ge; Kristin Stephan; Anke Jurisch; Stefan G Tullius; John Iacomini Journal: Proc Natl Acad Sci U S A Date: 2010-07-22 Impact factor: 11.205
Authors: Hilaire C Lam; Heng-Jia Liu; Christian V Baglini; Harilaos Filippakis; Nicola Alesi; Julie Nijmeh; Heng Du; Alicia Llorente Lope; Katherine A Cottrill; Adam Handen; John M Asara; David J Kwiatkowski; Issam Ben-Sahra; William M Oldham; Stephen Y Chan; Elizabeth P Henske Journal: Oncotarget Date: 2017-08-04