title: microRNA-21 regulates astrocytic response following spinal cord injury.
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 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.
authors.affiliation: Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. oneil-bhalala@fsm.northwestern.edu
authors.forename: Oneil G
authors.initials: OG
authors.lastname: Bhalala
authors.forename: Liuliu
authors.initials: L
authors.lastname: Pan
authors.forename: Vibhu
authors.initials: V
authors.lastname: Sahni
authors.forename: Tammy L
authors.initials: TL
authors.lastname: McGuire
authors.forename: Katherine
authors.initials: K
authors.lastname: Gruner
authors.forename: Warren G
authors.initials: WG
authors.lastname: Tourtellotte
authors.forename: John A
authors.initials: JA
authors.lastname: Kessler
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs