Open AccessDown-regulating Circular RNA Prkcsh suppresses the inflammatory response after spinal cord injury
Author(s) -
Jianan Chen,
Yining Zhang,
Lijie Tian,
Ying Zhang,
Xinyu Li,
Bin Ning
Publication year - 2022
Publication title -
neural regeneration research/neural regeneration research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.93
H-Index - 38
eISSN - 1876-7958
pISSN - 1673-5374
DOI - 10.4103/1673-5374.314114
Subject(s) - gene knockdown , spinal cord injury , spinal cord , tumor necrosis factor alpha , microrna , inflammation , medicine , gene expression , immunology , biology , cancer research , neuroscience , gene , genetics
Circular RNAs (circRNAs) are a class of conserved, endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation and are highly enriched in the nervous system. They participate in the survival and differentiation of multiple nerve cells, and may even promote the recovery of neurological function after stroke. However, their role in the inflammatory response after spinal cord injury remains unclear. In the present study, we established a mouse model of T9 spinal cord injury using the modified Allen's impact method, and identified 16,013 circRNAs and 960 miRNAs that were differentially expressed after spinal cord injury. Of these, the expression levels of circPrkcsh were significantly different between injured and sham-treated mice. We then treated astrocytes with tumor necrosis factor-α in vitro to simulate the inflammatory response after spinal cord injury. Our results revealed an elevated expression of circPrkcsh with a concurrent decrease in miR-488 expression in injured cells. We also found that circPrkcsh regulated the expression of the inflammation-related gene Ccl2. Furthermore, in tumor necrosis factor-α-treated astrocytes, circPrkcsh knockdown decreased the expression of Ccl2 by upregulating miR-488 expression, and reduced the secretion of inflammatory cytokines in vitro. These findings suggest that differentially expressed circRNAs participate in the inflammatory response after spinal cord injury and act as the regulators of certain microRNAs. Furthermore, circPrkcsh may be used as an miR-488 sponge to regulate Ccl2 expression, which might provide a new potential therapy for SCI. The study was approved by the Animal Ethics Committee of Shandong University of China (approval No. KYLL-20170303) on March 3, 2017.