Mechanisms of autophagy and apoptosis mediated by JAK2 signaling pathway after spinal cord injury of rats

• Published in: Experimental and therapeutic medicine Vol. 14; no. 2; pp. 1589 - 1593
• Main Authors: Xia, Yongzhi, Xia, Haijian, Chen, Dan, Liao, Zhengbu, Yan, Yi
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.08.2017; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: acute spinal cord injury; Apoptosis; Autophagy; Care and treatment; Catheters; Cell growth; Cytokines; Interleukins; JAK2/STAT3 signal pathway; Kinases; Messenger RNA; Proteins; Rodents; Signal transduction; Spinal cord injuries; Tumor necrosis factor-TNF; Beijing China; China; JAK2/STAT3 signal pathway; apoptosis; autophagy; acute spinal cord injury
• ISSN: 1792-0981; 1792-1015
• DOI: 10.3892/etm.2017.4674

The aim of this study was to investigate the pathogenesis of autophagy and apoptosis mediated by Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signal pathway after the onset of acute spinal cord injury (ASCI). A total of 45 Sprague-Dawley adult rats of either sex were selected for this study. The age of rats ranged from 8 to 10 weeks, and the average weight was 245 g. These rats were randomly divided into three groups, i.e. sham-operated group, model group, and the AG-490 intervention group (AG-490 is an inhibitor of JAK2). Each group contained 15 rats. Models were prepared using the modified Allen method. Five rats in each group were sacrificed at 6, 12 and 24 h, respectively, and the expression levels of p-JAK2 and p-STAT3 were detected in spinal cord tissue via western blot analysis. The levels of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected via ELISA, positive expression of light chain 3 (LC3)-II of microtubule-associated protein 1 via immunofluorescence labeling method, and mRNA expression levels of caspase-3 and Bax/Bcl-2 via RT-PCR. In the model group, the expression levels of p-JAK2, p-STAT3, IL-6, TNF-α and LC3-II, and the mRNA expression levels of caspase-3 and Bax/Bcl-2 at all time-points were significantly higher than those in the AG-490 intervention group, and the levels in the sham-operated group were the lowest (p<0.05). In the model group, peak levels of p-JAK2 and p-STAT3 were attained at 12 h, but a decline was seen at 24 h; while increasing trend was seen in other indicators. In conclusion, JAK2/STAT3 signal pathway can mediate the activity of autophagy and apoptosis in an early stage after the onset of ASCI of rat.