microRNA-21 regulates astrocytic response following spinal cord injury

Oneil G. Bhalala, Liuliu Pan, Vibhu Sahni, Tammy L. McGuire, Katherine Gruner, Warren G. Tourtellotte, John A. Kessler

Research output: Contribution to journalArticle

159 Scopus citations

Abstract

Astrogliosis following spinal cord injury (SCI) involves an early hypertrophic response that serves to repair damaged blood- brain barrier and a subsequent hyperplastic response that results in a dense scar that impedes axon regeneration. The mechanisms regulating these two phases of astrogliosis are beginning to be elucidated. In this study, we found that microRNA-21 (miR-21) increases in a timedependent manner following SCI in mouse. Astrocytes adjacent to the lesion area express high levels of miR-21 whereas astrocytes in uninjured spinal cord express low levels of miR-21. To study the role of miR-21 in astrocytes after SCI, transgenic mice were generated that conditionally overexpress either the primary miR-21 transcript in astrocytes or a miRNA sponge designed to inhibit miR-21 function. Overexpression of miR-21 in astrocytes attenuated the hypertrophic response to SCI. Conversely, expression of the miR-21 sponge augmented the hypertrophic phenotype, even in chronic stages of SCI recovery when astrocytes have normally become smaller in size with fine processes. Inhibition of miR-21 function in astrocytes also resulted in increased axon density within the lesion site. These findings demonstrate a novel role for miR-21 in regulating astrocytic hypertrophy and glial scar progression after SCI, and suggest miR-21 as a potential therapeutic target for manipulating gliosis and enhancing functional outcome.

Original languageEnglish (US)
Pages (from-to)17935-17947
Number of pages13
JournalJournal of Neuroscience
Volume32
Issue number50
DOIs
StatePublished - Dec 12 2012

ASJC Scopus subject areas

  • Neuroscience(all)

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    Bhalala, O. G., Pan, L., Sahni, V., McGuire, T. L., Gruner, K., Tourtellotte, W. G., & Kessler, J. A. (2012). microRNA-21 regulates astrocytic response following spinal cord injury. Journal of Neuroscience, 32(50), 17935-17947. https://doi.org/10.1523/JNEUROSCI.3860-12.2012