ABSTRACT
OBJECTIVE: This study aimed to construct miRNA co-expression network by using miRNA microarray data and screen the miRNAs associated with spinal cord injury (SCI) by comparative analysis, which might be considered as molecule labels for future forecasts or therapies. METHODS: We first downloaded SCI gene expression data GSE19890 from GEO (Gene Expression Omnibus), then constructed the miRNA co-expression network under three different states and analyzed the topologic attributes of network. After that, miRNAs associated with SCI were screened and subjected to function analysis by DAVID (Database for Annotation, Visualization and Integrated Discovery). RESULTS: In the co-expression network, miR-520a and miR-193b had the largest degree in the SCI and sham groups, respectively. A total of 22 differentially expressed miRNAs were identified. MiR-32 and miR-471 were the most significantly expressed in the SCI group compared with control and sham groups, respectively, which were newly reported to be related to SCI in this study. Function enrichment analysis of the target genes indicated that the screened miRNA were associated with cell adhesion, cytoplasmic vesicle and so on. CONCLUSIONS: MiRNAs identified in this study could be considered targets for SCI diagnosis and therapy.
Subject(s)
Gene Regulatory Networks , MicroRNAs/genetics , Spinal Cord Injuries/diagnosis , Spinal Cord Injuries/genetics , Female , Gene Regulatory Networks/physiology , Genetic Association Studies , Humans , Male , Microarray Analysis , Oligonucleotide Array Sequence AnalysisABSTRACT
To determine the level of brain-derived neurotrophic factor (BDNF) in experimental dog model of severe acute cauda equina syndrome, which was induced by multiple cauda equina constrictions throughout the entire lumbar (L), sacral (S) and coccygeal (Co) spinal cord and their central processes of the dorsal root ganglia neurons. Adult male mongrel dogs were randomly divided into 2 groups. The experiment group (n=4) was subjected to multiple cauda equina constrictions. The control group (n=4) was subjected to cauda equina exposure without constrictions. Level of BDNF in the spinal cord and the dorsal root ganglion cells (L7, S1-S3) was assessed 48 hours after multiple constrictions by immunohistochemical and histopathological analyses. 48 hours after multiple constrictions of cauda equina, up-regulation of BDNF within lumbosacral (L7-S3) spinal cord and dorsal root ganglion was observed in experimental group as compared to control group. Our result suggests that BDNF might play a role in the inflammatory and neuropathic pain as a result of multiple cauda equina constrictions. Regulation of BDNF level could potentially provide a therapy for treating cauda equina syndrome.
ABSTRACT
Osteoblasts play a crucial role in bone formation. However, the molecular mechanisms involved in osteoblast differentiation remain largely unclear. Runt-related gene 2 (Runx2) is a master transcriptional factor for osteoblast differentiation. Here we reported that p300/CBP-associated factor (PCAF) directly binds to Runx2 and acetylates Runx2, leading to an increase in its transcriptional activity. Upregulation of PCAF in MC3T3-E1 cells increases the expression of osteogenic marker genes including alkaline phosphatase (ALP), osteocalcin (Ocn), and Osteopontin (Opn), and ALP activity was stimulated as well. Consequently, the mineralization of MC3T3-E1 cells was remarkably improved by PCAF. In contrast, PCAF knockdown decreases the mRNA levels of ALP, Ocn, and Opn. ALP activity and the mineralized area were attenuated under PCAF knockdown conditions. These results indicate that PCAF is an important regulator for promoting osteoblast differentiation via acetylation modification of Runx2.
