MicroRNA381/Hes1 is a potential therapeutic target for spinal cord injury
The aim of the present study was to investigate whether microRNA381 is a potential therapeutic target for spinal cord injury (SCI) and its possible mechanism. Reverse transcription quantitative polymerase chain reaction (qPCR) for mRNA expression was used to analyze the changes of microRNA-381 expression. Cell viability and cell apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Caspase3 activity was measured using caspase3 activity kit, and western blot analysis was used to measure the protein expression of neurogenic locus notch homolog protein 1 (Notch1), notch 1 intracellular domain (NICD) and transcription factor HES-1 (Hes1). The data showed that microRNA381 expression of model SCI rats was downregulated compared with that of control rats. Overexpression of microRNA381 promoted cell proliferation, and inhibited apoptosis and caspase3 and apoptosis regulator BAX (Bax) protein expression in neurocytes. Overexpression of microRNA381 also increased Wnt and βcatenin protein expression, and suppressed the protein expression of Notch1, NICD and Hes1 in neurocytes. Wnt inhibitor, WntC59 (1 µmol/l), inhibited cell proliferation, promoted apoptosis and caspase3 and Bax protein expression, suppressed βcatenin protein expression and induced Hes1 protein expression in neurocytes following microRNA381 overexpression. Notch inhibitor, FLI06 (1 µmol/l), promoted cell proliferation, inhibited apoptosis and caspase3 and Bax protein expression, and suppressed NICD and Hes1 protein expression in neurocytes following microRNA381 overexpression. Thus, this study showed that overexpression of microRNA381 promotes cell proliferation of neurocytes in SCI via Hes1 expression, which may be a novel important mechanism for SCI in clinical applications.
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Document Type: Research Article
Affiliations: Department of Orthopedics, The General Hospital of Tianjin Medical University, Heping, Tianjin 300052, P.R. China
Publication date: January 1, 2018
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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