Microarray Expression Profile of lncRNAs and mRNAs in Rats with Traumatic Brain Injury after A2B5+ Cell Transplantation

Abstract

Traumatic brain injury (TBI) may cause neurological damage, but an effective therapy and the associated mechanisms of action have not yet been elucidated. A TBI model was established using the modified Feeney method. A2B5+ cells, an oligodendroglial progenitor, were acquired from induced pluripotent stem cells (iPSCs) by mouse embryonic fibroblasts and were transplanted into the injured site. The neurological severity score (NSS) was recorded on 3 d, 7 d, 11 d, 15 d, and 19 d. Seven days after transplantation, oligodendrocytes 2 (Olig2) and myelin basic protein (MBP) were detected by immunohistochemistry (IHC) and Western blot (WB), and long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) were screened by microarray technology. Moreover, we took an intersection of the differentially expressed lncRNAs or mRNAs and scanned 10 kb upstream and downstream of the common lncRNAs. Meanwhile, Gene Ontology (GO) and pathway analysis on mRNAs was performed in the A2B5+ iPSC group. A2B5+ iPSCs survived and migrated around the injury site and differentiated into oligodendrocytes. Meanwhile, the increase in Olig2 and MBP were higher in A2B5+ cell-engrafted rats than that in TBI rats. However, the NSSs in the A2B5+ iPSC group were lower than that in the TBI group. Between the TBI and sham groups, 270 lncRNAs and 1,052 mRNAs were differently expressed (P < 0.05, fold change (FC) > 2), while between the A2B5+ iPSC and TBI groups, 83 lncRNAs and 360 mRNAs were differently expressed (P < 0.05, FC > 2). Meanwhile, 37 lncRNAs and 195 mRNAs were simultaneously changed in the 2 parts. Using bioinformatic analysis, we found the crucial lncRNA and mRNA were ENSRNOT00000052577 and Kif2c in the TBI brain with cell transplantation. This study demonstrated that A2B5+ iPSC grafts effectively improved neurological function, and the mechanism of action was associated with lncRNA and mRNA expression. Therefore, A2B5+ iPSC transplantation could be considered as a new method for the treatment of TBI, and ENSRNOT00000052577 and Kif2c may be new molecular targets or markers for functional improvement.

Microarray Expression Profiles of lncRNAs and mRNAs in Postoperative Cognitive Dysfunction

“…Microarray was used to investigate differentially expressed lncRNAs and mRNAs which then become the main data for the subsequent bioinformatics analyses of the study. This working strategy has been applied and validate in studying many diseases including cancer ( Han et al, 2018 ; Liang et al, 2018 ; Lou et al, 2018 ), cerebral ischemia-induced lung injury ( Hu et al, 2017 ), and traumatic brain injury ( Lyu et al, 2017 ). In our study, microarray was used to study the changes in expression of lncRNAs and mRNAs in POCD group.…”

Literature-Based Enrichment Insights into Redox Control of Vascular Biology

“…ZFAS1 was also determined to be a potential biomarker for coronary artery disease/acute myocardial infarction [153]. Lyu et al also showed ZFAS1 to be upregulated in rats with traumatic brain injury [154]. This shows that miR-27b has been linked to OS and vascular disease and that ZFAS1 has been linked to vascular disease but its possible role in the fine-tuning of miR-27b in these pathologies have not been explored.…”

On the Viability and Potential Value of Stem Cells for Repair and Treatment of Central Neurotrauma: Overview and Speculations

“…Since then, iPSCs have become an attractive source of pluripotent stem cells for use in neural replacement and regeneration therapies, given their potential to generate a “virtually limitless supply” of autologous iPSCs—thus resolving ethical concerns regarding the source of stem cells and risks associated with immunological rejection in transplant recipients ( 11 , 196 ). In neural therapies, iPSCs and their progeny can facilitate regeneration of neurons, induce axonal remyelination, provide trophic support and immunomodulation, and modify the extracellular microenvironment ( 105 , 167 , 177 , 187 ).…”