Trem1 mediates neuronal apoptosis via interaction with SYK after spinal cord ischemia-reperfusion injury.

ABSTRACT

OBJECTIVE: This research aimed to study the impact and regulatory mechanism of Trem1 in spinal cord ischemia-reperfusion injury (SCIRI). METHOD: Temporary aortic cross clamp followed by reperfusion was used to establish SCIRI mice model. Mice motion function was estimated by Basso, Beattie, Bresnahan (BBB) score. Spinal cord infract zone was analyzed by HE and TUNEL staining. High throughput sequencing was performed to explore potential target for SCIRI. N2a cells were used to simulate the pathophysiological process of SCIRI in vitro with oxygen-glucose-serum deprivation/restoration (OGSD/R). RT-PCR and Western blot were token to determine mRNA and protein expression levels. Knockdown of Trem1 was performed with siRNA transfection in vitro and shRNA adenovirus injection in vivo. The relationship between Trem1 and SYK was analyzed by immunoprecipitation and immunofluorescence. RESULT: We observed that neuronal apoptosis of spinal cord was aggravated after SCIRI. Trem1 expression was dramatically upregulated as shown by high throughput sequencing, RT-PCR and Western blot results. Furthermore, Trem1 triggered apoptosis of N2a cells induced by OGSD/R, and knockdown of Trem1 by siRNAs blocked apoptosis via PI3K/AKT and NF-κB signaling pathway by interacting with SYK. In addition, we found that intrathecal injection of adenovirus with Trem1 shRNA could downregulate SYK and inhibit neuron apoptosis caused by SCIRI in vivo. CONCLUSION: Trem1 interacts with SYK and mediates neuronal apoptosis via the PI3K/AKT and NF-κB signaling pathway. Trem1 may be a therapeutic candidate for patients with SCIRI.