Long Noncoding RNA ISA1 Protects Against Ischemic Brain Damage by Promoting the Transformation of Microglia Toward Anti-inflammatory Phenotype via the SOCS3/JAK2/STAT3 Pathway

Abstract

The shift of microglia towards an anti-inflammatory phenotype has been shown to decrease neuroinflammation, improve neurological function, and is considered a potential therapeutic approach for stroke. Abnormal expression of multiple long noncoding RNA (LncRNA) has been discovered to be crucially related to the pathogenesis progress of ischemic brain injury. Here we concentrated on a novel LncRNA NR_037961.1, which we named ischemic stroke associated LncRNA1 (LncRNA ISA1). The expression of LncRNA ISA1 was notably decreased in brain tissue of middle cerebral artery occlusion (MCAO) mice. Overexpression of LncRNA ISA1 decreases cerebral infarction and brain edema, and improves cerebral blood flow and neurological outcome, promoting recovery of MCAO mice. Additionally, the neuroprotective effects that LncRNA ISA1 plays on MCAO mice are mediated by encouraging the transformation of microglia toward anti-inflammatory phenotype and alleviating neuroinflammation. LncRNA ISA1 facilitates the phenotypic transformation of microglia, closely linked to its promotion of SOCS3 expression and subsequent inhibition of the JAK2/STAT3 signaling pathway. Furthermore, downregulation of SOCS3 eliminated the effects of LncRNA ISA1 on transformation of microglia to anti-inflammatory phenotype. Our results indicate that LncRNA ISA1 promotes the anti-inflammatory polarization of microglia via regulation of the SOCS3/JAK2/STAT3 signaling pathway, and contributes to its neuroprotective effects in ischemic stroke.