MicroRNA Dysregulation in the Spinal Cord following Traumatic Injury

Abstract

Spinal cord injury (SCI) triggers a multitude of pathophysiological events that are tightly regulated by the expression levels of specific genes. Recent studies suggest that changes in gene expression following neural injury can result from the dysregulation of microRNAs, short non-coding RNA molecules that repress the translation of target mRNA. To understand the mechanisms underlying gene alterations following SCI, we analyzed the microRNA expression patterns at different time points following rat spinal cord injury.The microarray data reveal the induction of a specific microRNA expression pattern following moderate contusive SCI that is characterized by a marked increase in the number of down-regulated microRNAs, especially at 7 days after injury. MicroRNA downregulation is paralleled by mRNA upregulation, strongly suggesting that microRNAs regulate transcriptional changes following injury. Bioinformatic analyses indicate that changes in microRNA expression affect key processes in SCI physiopathology, including inflammation and apoptosis. MicroRNA expression changes appear to be influenced by an invasion of immune cells at the injury area and, more importantly, by changes in microRNA expression specific to spinal cord cells. Comparisons with previous data suggest that although microRNA expression patterns in the spinal cord are broadly similar among vertebrates, the results of studies assessing SCI are much less congruent and may depend on injury severity. The results of the present study demonstrate that moderate spinal cord injury induces an extended microRNA downregulation paralleled by an increase in mRNA expression that affects key processes in the pathophysiology of this injury.

miRNA-138 regulates MLK3/JNK/MAPK pathway to protect BV-2 cells from H2O2-induced apoptosis

“…In addition to MLK3, possible targets of miR-138 also include apoptosis-related genes like caspase-3, calpain 1, calpain 2, Bcl-2, c-Myc, and apoptosis-inducing factor (AIF) (8,25). Some of these target genes were reported to be involved in the pathological process of SCI.…”

“…Recently, the role of the miRNAs in SCI development and their value in SCI diagnosis were reported in several papers (5)(6)(7). The microarray analysis revealed that miR-138 expression was signifi cantly enriched in the adult rat spinal cord following SCI (8). Mixed-lineage kinase 3 (MLK3) contains seeding sequences of miR-138 in its 3'-untransltaed region (UTR) and was proved to be a direct target of miR-138 (9).…”

miRNA Control of Tissue Repair and Regeneration

“…11 After spinal cord injury in Wistar rats, miRNA expression is markedly subdued from day 3 after injury with gradual rebound of down-regulated miRNA at 7 days after injury. 12 Suppression of miRNA expression after spinal cord injury was verified in an independent study in which downregulated miRNAs were reported up to 14 days after injury. 13 The pattern of miRNA suppression after injury holds across organ systems.…”

Altered MicroRNA Expression in the Ischemic^|^ndash;Reperfusion Spinal Cord With Atorvastatin Therapy

“…A number of microRNAs were found in the mammalian brain and spinal cord, where they are involved in the regulation of several nervous diseases (1). Recently, several reports have revealed important roles of microRNAs in traumatic SCI (2,3). We here describe for the first time microRNA expression profiling of ischemic rat spinal cord in the context of pre-treatment with atorvastatin using a quantitative real-time PCR based array.…”