Identification of the Fosl1/AMPK/autophagy axis involved in apoptotic and inflammatory effects following spinal cord injury.

Strategies for reducing spinal cord injury (SCI) have become a research focus because an effective treatment of SCI is unavailable. The objective of this study was to explore the underlying mechanisms of Fosl1 following SCI. Based on the analysis of the Gene Expression Omnibus (GEO) database, Fosl1 was found to be highly enhanced in SCI. This result was confirmed in our animal model, and Fosl1 was found to be obviously expressed in neurons. Next, we treated PC-12 cells with HO to mimic injured neurons and further verified that Fosl1 silencing upregulated AMPK expression, promoted autophagy and inhibited inflammation and apoptosis. Subsequently, a special inhibitor of AMPK was used to examine the role of AMPK, and we learned that the inhibition of AMPK suppressed autophagy and promoted inflammation and apoptosis following Fosl1 silencing. These changes completely reversed the beneficial effects of Fosl1 silencing on injured PC-12 cells. Moreover, treatment with an AMPK activator resulted in effects that were opposite those of the inhibitor. Finally, rats were injected intrathecally with si-Fosl1 to detect its role in vivo. The results showed that si-Fosl1 improved neurological function and decreased apoptosis and inflammation at 14 d postoperation, and the activator further benefited the rats of si-Fosl1 treatment. In conclusion, Fosl1 inhibits autophagy and promotes inflammation and apoptosis through the AMPK signaling pathway following SCI in vivo and in vitro.