Administration of Antagomir-223 Inhibits Apoptosis, Promotes Angiogenesis and Functional Recovery in Rats with Spinal Cord Injury

• Published in: Cellular and molecular neurobiology Vol. 35; no. 4; pp. 483 - 491
• Main Authors: Liu, Da, Huang, Ying, Jia, Changqing, Li, Yan, Liang, Feng, Fu, Qin
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.05.2015
• Subjects: Animals; Antagomirs; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Biomedical and Life Sciences; Biomedicine; Caspase 3 - metabolism; Cell Biology; Injections, Spinal; Male; MicroRNAs - genetics; MicroRNAs - metabolism; Neovascularization, Physiologic - drug effects; Neurobiology; Neurosciences; Oligonucleotides - administration & dosage; Oligonucleotides - pharmacology; Original Research; Rats, Sprague-Dawley; Receptors, AMPA - metabolism; Recovery of Function - drug effects; Spinal Cord Injuries - physiopathology; Up-Regulation - drug effects; Spinal cord injury (SCI); Angiogenesis; Antagomir-223; Functional recovery; Apoptosis
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-014-0142-x

MicroRNAs (miRNAs) are recently described as a class of short non-coding RNAs, which play important roles in post-transcriptional gene regulation and involved in many physiological and pathological processes. MicroRNA-223 (miR-223) has been showed highly elevated in the injured spinal cord. However, the potential role and underlying mechanisms of miR-223 in spinal cord injury (SCI) were incompletely understood. In the present study, we observed the persistent high levels of miR-223 in the injured spinal cord at different time points (1, 3, 7, and 14 days) after SCI. Besides, inhibiting miR-223 by intrathecally injection with antagomir-223 significantly improved recovery in hindlimb motor function and attenuated cell apoptosis in spinal cord-injured rats. Additionally, antagomir-223 treatment markedly decreased the pro-apoptotic protein levels, including Bax and cleaved caspase-3, up-regulated the anti-apoptotic Bcl-2 protein level, as well as the expression of GluR2. Moreover, inhibition of miR-223 promoted angiogenesis, as evidenced by the increased CD31 expression and microvascular density. Taken together, our results indicate that inhibition of miR-223 with antagomir-223 exerts protective role in functional recovery, angiogenesis, and anti-apoptosis during SCI. Thereby, miR-223 may be a promising target of therapy for SCI.