Protection of rats spinal cord ischemia-reperfusion injury by inhibition of MiR-497 on inflammation and apoptosis: Possible role in pediatrics.
MicroRNAs are extensively included in the pathogenesis and progression of many diseases by inhibiting target gene expression. Recently, studies have demonstrated that microRNA-497 (miR-497) may be implicated in human breast cancer that miR-497 predicts the prognosis of breast cancer patients from the posttranscriptional level. However, the specific function of miR-497 in spinal cord ischemia-reperfusion (IR) injury is far from clear nowadays. The present study was designed to determine the role of miR-497 in spinal cord IR injury and investigate the underlying spinal cord protective mechanism. The rat spinal cord IR injury model was performed by occluding the left anterior descending coronary artery for 30 min, which is then followed by 12h reperfusion. As predicted, miR-497 over-expression markedly decreased the expression of IL-1 receptor associated kinase (IRAK1) and Cyclic AMP response element binding protein (CREB). Moreover, Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) and Caspase-3, as miR-497 potential targets were significantly suppressed after miR-497 transfection, then preventing inflammatory cytokines and factors regulating apoptosis. We also found that tumor necrosis factor-a (TNF-α) and interleukin-1beta (IL-1β) activity, pro-apoptotic related genes, such as extracellular regulated protein kinases (ERK), Bcl-2 Associated X Protein (Bax), Bcl-2, Bcl-xL levels were all decreased associated with the down-regulation of IRAK1 and CREB. In conclusion, our data demonstrate that miR-497 could inhibit inflammation and apoptosis of spinal cord IR through its targets, IRAK1 of TLR4 and CREB signaling pathway. Thus, miR-497 may constitute a new therapeutic target for the prevention of spinal cord IR injury.
Department of Pediatric Surgery, Yishui Central Hospital, Linyi, Shandong 276400, China.
Meng
M
Xu
Department of Pediatric Surgery, Yishui Central Hospital, Linyi, Shandong 276400, China.
Hai-Feng
HF
Wang
Department of Hand and Foot Surgery, Yishui Central Hospital, Linyi, Shandong 276400, China.
Ying-Ying
YY
Zhang
Department of Pediatric Surgery, Yishui Central Hospital, Linyi, Shandong 276400, China.
Hui-Wen
HW
Zhuang
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D007278:Injections, Spinal; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D010372:Pediatrics; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology*; D013116:Spinal Cord / Q000098:blood supply* / Q000473:pathology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D018836:Inflammation Mediators; C000609693:MIRN497 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; D018696:Neuroprotective Agents; D051197:Toll-Like Receptor 4; C547807:IRAK1 protein, rat; D053592:Interleukin-1 Receptor-Associated Kinases
CREB; IRAK1; Spinal cord ischemia–reperfusion; TLR4; miR-497