Long non-coding RNA CHRF accelerates LPS-induced acute lung injury through microRNA-146a/Notch1 axis.
Ann Transl Med
; 9(16): 1299, 2021 Aug.
Article
in En
| MEDLINE
| ID: mdl-34532436
ABSTRACT
BACKGROUND:
The present study sought to investigate the regulatory role of the long non-coding RNA (lncRNA) cardiac hypertrophy-related factor (CHRF) in a mouse model of acute lung injury (ALI) and in primary mouse pulmonary microvascular endothelial cells (MPVECs) treated with lipopolysaccharide (LPS).METHODS:
C57BL/6 mice were given adenovirus (Ad) sh-CHRF or negative control (NC) before undergoing cecal ligation and perforation. MPVECs transfected with Adsh-CHRF or NC were treated with LPS. Double luciferase assay was used to detect the binding of miR-146a to CHRF or Notch1. Subsequently, MPVECs were co-transfected with miR-146a inhibitor and sh-CHRF for 24 hours, and then treated with LPS.RESULTS:
High expression of CHRF was detected in septic mice. Cecal ligation and perforation induced ALI and apoptosis in mice, whereas, CHRF knockout could inhibit ALI. The protein expression levels of TNF-α, IL-1ß and IL-6 in the lung and bronchoalveolar lavage fluid of the CLP group were up-regulated, whereas the expression of IL-4 and IL-10 was down-regulated. CHRF inhibition reduced the production of proinflammatory cytokines in septic mice. The inhibitory effect of CHRF gene knockdown on lung inflammation and apoptosis was confirmed in the septic cell model. Mechanistic investigation showed that CHRF up-regulated the level of Notch1 by sponging miR-146a. Additionally, the low expression of miR-146a reversed the inhibitory effect of CHRF gene knockout on LPS-induced inflammatory response and apoptosis. Together, in vivo and in vitro results demonstrated that CHRF enhanced sepsis-induced ALI by targeting miR-146a and up-regulating Notch1.CONCLUSIONS:
CHRF can induce inflammation and apoptosis caused by sepsis by miR-146a/Notch1 axis. Therefore, it may serve as a potential drug target for treating sepsis-induced ALI.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Prognostic_studies
Language:
En
Journal:
Ann Transl Med
Year:
2021
Document type:
Article
Affiliation country:
China