4.7 Article

Gene Expression Analysis of the Effect of Ischemic Infarction in Whole Blood

Journal

Publisher

MDPI
DOI: 10.3390/ijms18112335

Keywords

stroke; middle cerebral artery occlusion model; gene expression analysis; messenger RNA; microRNA; rat

Funding

  1. Japan Society for the Promotion of Science (JSPS) [26750202]
  2. Council for Science, Technology and Innovation (CSTI), Cross-Ministerial Strategic Innovation Promotion Program (SIP), Technologies for Creating Next-generation Agriculture, Forestry and Fisheries
  3. Grants-in-Aid for Scientific Research [17H01962, 26750202, 16H04919] Funding Source: KAKEN

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Given the abundance of stroke patients and deaths from stroke worldwide, many studies concerning the aftermath of stroke are being carried out. To reveal the precise effect of ischemic infarction, we conducted a comprehensive gene expression analysis. Alongside a middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model, we used a group undergoing sham surgery for comparison, which was the same as MCAO surgery but without blood vessel occlusion. Subsequently, infarction of the brains of MCAO-treated rats occurred, but did not occur in the sham-treated rats. Using whole blood, we carried out DNA microarray analysis, revealing the gene expression alterations caused by stroke. Downregulation of immune pathways and cluster of differentiation (CD) molecules indicated immunodepression. By conducting miRNA microarray analysis, we extracted seven miRNAs as significantly regulated: miR-107-5p, miR-383-5p, miR-24-1-5p, mir-191b, miR-196b-5p, and miR-3552 were upregulated, and mir-194-1 was downregulated. Among these seven miRNAs, three had one target mRNA each that was extracted as differentially expressed, and the expression levels of all pairs were inversely correlated. This indicates the occurrence of miRNA-mRNA regulatory systems in blood: between miR-107-5p and H2A histone family member Z (H2afz), miR-196b-5p and protein tyrosine phosphatase receptor type C (Ptprc), and miR-3552 and serine/arginine-rich splicing factor 2 (Srsf2). Moreover, six miRNAs had matching human miRNAs with similar sequences, which are potential human stroke biomarkers.

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