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lncRNA Mtss1 promotes inflammatory responses and secondary brain injury after intracerebral hemorrhage by targeting miR-709 in mice.

Abstract：

:Secondary brain injuries following intracerebral hemorrhage (ICH) are mediated by inflammatory pathway activation. The present study aimed to characterize long noncoding RNAs (lncRNAs) that are differentially expressed in cerebral tissues during ICH pathogenesis and to investigate their pathogenic functions. An ICH mouse model established by collagenase injection was used to obtain differentially expressed lncRNAs for deep sequencing. A cellular inflammation model was established by treating mouse microglia with lipopolysaccharide. Expression of lncRNA and miRNA was assessed by quantitative RT-PCR, and protein abundance was measured by western blot. Cytokine levels in mouse serum and cell culture supernatants were analyzed using enzyme-linked immunosorbent assay. Cerebral injury was evaluated by hematoxylin-eosin and Nissl staining, the ratio of brain dry weight/brain wet weight, and neurobehavior scoring. Ionized calcium-binding adaptor molecule 1 (IBA1) expression in the brain sections was assessed using immunohistochemistry. A total of 3681 lncRNAs were differentially expressed in the brain tissue of the ICH mice group compared with the Sham group. Of these, lncRNA metastasis suppressor-1 (Mtss1) expression was increased. Mtss1 knockdown by siRNA in the cellular model strongly suppressed TIR-domain-containing adapter-inducing interferon-β (TRIF) expression, P65 phosphorylation, and tumor necrosis factor (TNF)-α and interleukin (IL)-1β secretion. Mtss1 knockdown in ICH mice inhibited secondary brain injury and decreased IBA1, TNF-α, and IL-1β. Mtss1 was predicted to bind miR-709, and Mtss1 knockdown elevated miR-709 expression in the cellular inflammation model and ICH mice. High expression of Mtss1 promoted inflammatory brain injuries after ICH by enhancing inflammatory cytokine secretion and targeting miR-709 expression.

journal_name

Brain Res Bull

journal_title

Brain research bulletin

authors

Chen JX,Wang YP,Zhang X,Li GX,Zheng K,Duan CZ

doi

10.1016/j.brainresbull.2020.04.017

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

20-29

eissn

0361-9230

issn

1873-2747

pii

S0361-9230(20)30144-1

journal_volume

162

pub_type

杂志文章

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lncRNA Mtss1 promotes inflammatory responses and secondary brain injury after intracerebral hemorrhage by targeting miR-709 in mice.