First Author | Bhalala OG | Year | 2012 |
Journal | J Neurosci | Volume | 32 |
Issue | 50 | Pages | 17935-47 |
PubMed ID | 23238710 | Mgi Jnum | J:192021 |
Mgi Id | MGI:5463825 | Doi | 10.1523/JNEUROSCI.3860-12.2012 |
Citation | Bhalala OG, et al. (2012) microRNA-21 regulates astrocytic response following spinal cord injury. J Neurosci 32(50):17935-47 |
abstractText | 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. |