Rapamycin suppresses hypoxia/reoxygenation-induced islet injury by up-regulation of miR-21 via PI3K/Akt signalling pathway.
OBJECTIVE
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.


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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Department of Hepatobiliopancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China.
Yi
Y
Zhang
Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, China.
Sirong
S
He
Department of Hepatobiliopancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China.
Xiaojion
X
Du
Department of Emergency, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yaowen
Y
Jiang
Department of Hepatobiliopancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China.
Bole
B
Tian
Department of Emergency, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Shuyun
S
Xu
D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000628:therapy; D015536:Down-Regulation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous; D015854:Up-Regulation / Q000187:drug effects*
D000070416:Antagomirs; D007166:Immunosuppressive Agents; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D020123:Sirolimus
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