TY - JOUR T1 - microRNA-21 Regulates Astrocytic Response Following Spinal Cord Injury JF - The Journal of Neuroscience JO - J. Neurosci. SP - 17935 LP - 17947 DO - 10.1523/JNEUROSCI.3860-12.2012 VL - 32 IS - 50 AU - Oneil G. Bhalala AU - Liuliu Pan AU - Vibhu Sahni AU - Tammy L. McGuire AU - Katherine Gruner AU - Warren G. Tourtellotte AU - John A. Kessler Y1 - 2012/12/12 UR - http://www.jneurosci.org/content/32/50/17935.abstract N2 - 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 time-dependent 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. ER -