MicroRNA‐22‐3p alleviates spinal cord ischemia/reperfusion injury by modulating M2 macrophage polarization via IRF5. Issue 1 (8th June 2020)

• Record Type: Journal Article
• Authors: Fang, Hua; Yang, Miao; Pan, Qin; Jin, Hon‐Ling; Li, Hua‐Feng; Wang, Ru‐Rong; Wang, Quan‐Yun; Zhang, Jian‐Ping
• Is Part Of: Journal of neurochemistry. Volume 156:Issue 1(2021)
• Page Start: 106
• Page End: 120
• Publication Date: 2020-06-08
• Subjects: interferon regulatory factor 5 -- ischemia/reperfusion -- M2 polarization -- macrophages -- microRNA‐22‐3p -- spinal cord injury; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.15042
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract : Abstract: Cell death after spinal cord ischemia/reperfusion (I/R) can occur through necrosis, apoptosis, and autophagy, resulting in changes to the immune environment. However, the molecular mechanism of this immune regulation is not clear. Accumulating evidence indicates that microRNAs (miRs) play a crucial role in the pathogenesis of spinal cord I/R injury. Here, we hypothesized miR‐22‐3p may be involved in spinal cord I/R injury by interacting with interferon regulatory factor (IRF) 5. Rat models of spinal cord I/R injury were established by 12‐min occlusion of the aortic arch followed by 48‐hr reperfusion, with L4‐6 segments of spinal cord tissues collected. MiR‐22‐3p agomir, a lentivirus‐delivered siRNA specific for IRF5, or a lentivirus expressing wild‐type IRF5 was injected intrathecally to rats with I/R injury to evaluate the effects of miR‐22‐3p and IRF5 on hindlimb motor function. Macrophages isolated from rats were treated with miR‐22‐3p mimic or siRNA specific for IRF5 to evaluate their effects on macrophage polarization. The levels of IL‐1β and TNF‐α in spinal cord tissues were detected by ELISA. miR‐22‐3p was down‐regulated, whereas IRF5 was up‐regulated in rat spinal cord tissues following I/R. IRF5 was a target gene of miR‐22‐3p and could be negatively regulated by miR‐22‐3p. Silencing IRF5 or over‐expressing miR‐22‐3p relieved inflammation, elevated Tarlov score, and reduced the degree of severity of spinal cord I/R injury. Increased miR‐22‐3p facilitated M2 polarization of macrophages and inhibited inflammation in tissues by inhibiting IRF5, thereby attenuating spinal cord I/R injury. Taken together, these results demonstrate that increased miR‐22‐3p can inhibit the progression of spinal cord I/R injury by repressing IRF5 in macrophages, highlighting the discovery of a promising new target for spinal cord I/R injury treatment. Abstract : MicroRNA‐22‐3p can reduce spinal cord ischemia–reperfusion injury by regulating interferon regulatory factor 5 to promote M2 polarization of macrophages. Rat models of spinal cord ischemia/reperfusion injury were established by 12‐min occlusion of the aortic arch followed by 48‐hr reperfusion. MicroRNA‐22‐3p and interferon regulatory factor 5 were over‐expressed or silenced in rats to evaluate their effects on hindlimb motor function. MicroRNA‐22‐3p was down‐regulated, whereas interferon regulatory factor 5 was up‐regulated in rat spinal cord tissues following ischemia/reperfusion. Interferon regulatory factor 5 was targeted by microRNA‐22‐3p. Silencing interferon regulatory factor 5 or increasing microRNA‐22‐3p relieved inflammation, facilitated M2 polarization of macrophages. Therefore, increased microRNA‐22‐3p can inhibit progression of spinal cord ischemia/reperfusion injury by repressing interferon regulatory factor 5 in macrophages.