Downregulation of LncRNA Gas5 inhibits apoptosis and inflammation after spinal cord ischemia-reperfusion in rats.

Abstract:

:Spinal cord ischemia-reperfusion injury(SCII)affects nerve function through many mechanisms, which are complex and not fully understood. Recently, accumulating evidence has indicated that long noncoding RNAs (lncRNAs) play an increasingly important role in SCII. We investigated the role of lncRNA growth arrest-specific 5(Gas5) in a rat SCII model, and its effects on apoptosis and inflammation possibly by modulating MMP-7, cleaved caspase-3 and IL-1β. LncRNA Gas5 and MMP-7 were knocked down by intrathecal siRNA injection. Neurological assessment and TUNEL assay were performed. The RNA and protein expression levels of lncRNA Gas5, MMP-7, cleaved caspase-3 and IL-1β were determined by PCR and Western blotting, respectively. MMP-7 localization was visualized by double-immunofluorescence. SCII induced functional impairment in the hind limb, and the expression of lncRNA Gas5 was highest at 24 h after SCII. LncRNA Gas5 downregulation inhibited the RNA and protein expression of MMP-7, as well as the protein expression of cleaved caspase-3 and IL-1β. LncRNA Gas5 downregulation reduced the number of TUNEL-positive and MMP-7-positive double-labeled cells. Therefore, lncRNA Gas5 downregulation alleviated hind limb functional impairment and improved neuronal apoptosis after SCII. MMP-7 downregulation also inhibited apoptosis and inflammation and alleviated damage. Pretreatment with intrathecal injection of si-lncRNA Gas5 and si-MMP-7 reduced the expression levels of cleaved caspase-3 and IL-1β, protecting nerve function after SCII. These results show that lncRNA Gas5 plays an important role in SCII, perhaps by inhibiting MMP-7, cleaved caspase-3 and IL-1β. LncRNA Gas5 downregulation could be a promising therapeutic approach in the SCII treatment.

journal_name

Brain Res Bull

journal_title

Brain research bulletin

authors

Zhang Z,Li X,Chen F,Li Z,Wang D,Ren X,Ma H

doi

10.1016/j.brainresbull.2020.12.005

subject

Has Abstract

pub_date

2020-12-11 00:00:00

pages

110-119

eissn

0361-9230

issn

1873-2747

pii

S0361-9230(20)30714-0

journal_volume

168

pub_type

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