The transcription factor Foxd3 induces spinal cord ischemia-reperfusion injury by potentiating microRNA-214-dependent inhibition of Kcnk2

Abstract

Spinal cord injury after surgical repair of the thoracic or thoracoabdominal aorta is a devastating complication that is associated with pathological changes, including inflammation, edema, and nerve cell damage. Recently, microRNA (miRNA)-modulated control of spinal cord injury has been actively investigated. This study aims to clarify the regulatory effect of miR-214-mediated inhibition of Kcnk2 following spinal cord ischemia-reperfusion injury (SCII) and the possible underlying mechanisms. SCII was induced in rats by occluding the aortic arch followed by reperfusion. Gain-of-function and loss-of-function experiments were conducted to explore the modulatory effects of Foxd3, miR-214 and Kcnk2 on PC12 cells under hypoxia/reoxygenation (H/R) conditions. MiR-214 and Kcnk2 were poorly expressed, while Foxd3 was highly expressed in the rat spinal cord tissues and H/R-treated PC12 cells. Kcnk2 overexpression enhanced the viability and inhibited the apoptosis of the H/R-treated PC12 cells. Notably, Foxd3 activated miR-214, and miR-214 targeted Kcnk2. In addition, upregulation of Kcnk2 or knockdown of Foxd3 promoted the cell viability and reduced the apoptosis of the H/R-treated PC12 cells. Overall, our study identified a novel mechanism of Foxd3/miR-214/Kcnk2 involving SCII, suggesting that either Foxd3 or miR-214 may be a novel target for the treatment of SCII.

Neurology: Seeking salvation for spines after surgery

Therapeutic strategies that protect neurological function could prevent serious side effects associated with surgery of the aorta. Patients undergoing aortic surgery for aneurysm or other conditions are at risk of spinal cord damage associated with reduced blood flow during surgery and the subsequent restoration of normal circulation. Researchers led by Fei Yin at Jilin University in Changchun, China, have identified molecular mechanisms that can potentially increase this neurological harm. They show that the combination of low oxygen and reperfusion triggers production of a protein called Foxd3, which switches off cellular pathways that otherwise protect and repair vulnerable tissues. By interfering with this Foxd3-mediated response, Yin’s team was able to protect motor function and preserve the survival of spinal cord neurons in a rat model of this condition, suggesting a potential therapeutic avenue for heart surgery patients.