miR-19a-3p inhibition alleviates sepsis-induced lung injury via enhancing USP13 expression
| Autor: | Hangqi Ren, Qiaolian Xu, Wei Mu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide Interleukin-1beta Lung injury Real-Time Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Cell Line Proinflammatory cytokine Sepsis Mice chemistry.chemical_compound Animals Medicine Gene knockdown Lung Interleukin-6 Tumor Necrosis Factor-alpha business.industry Antagomirs Lung Injury Transfection medicine.disease Mice Inbred C57BL Systemic inflammatory response syndrome Disease Models Animal MicroRNAs medicine.anatomical_structure chemistry Gene Knockdown Techniques Cancer research Cytokines Ubiquitin-Specific Proteases business |
| Zdroj: | Acta Biochimica Polonica. |
| ISSN: | 1734-154X 0001-527X |
| DOI: | 10.18388/abp.2020_5505 |
| Popis: | Sepsis is a systemic inflammatory response syndrome caused by various pathogenic microorganisms or toxins. Lung damage is one of the causes of death in patients with sepsis. This study aimed to investigate the role of miR-19a-3p and its regulation mechanism in sepsis-induced lung injury. MH-S cells were treated with lipopolysaccharide (LPS) to establish sepsis-induced lung injury cell model. C57BL/6 mice were injected with miR-19a-3p antagomiR and LPS to construct animal model. LPS-treated and control cells were transfected with miR-19a-3p mimic, miR-19a-3p inhibitor or USP13 expression vector . The expression levels of miR-19a-3p and USP13 were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The concentration of inflammatory cytokines was measured with enzyme-linked immunosorbent assay (ELISA). The relationship of miR-19a-3p and USP13 was validated using dual-luciferase reporter assay. The lung damage was assessed with hematoxylin-eosin staining (HE). The results showed that LPS treatment increased the concentration of TNF-α, IL-6 and IL-1β in MH-S cells. In LPS treated MH-S cells, the level of miR-19a-3p gradually increased over time. Both miR-19a-3p knockdown and USP13 overexpression in MH-S cells inhibited the LPS-induced production of TNF-α, IL-6 and IL-1β. Moreover, miR-19a-3p negatively regulated the expression of USP13 in MH-S cells. Furthermore, miR-19a-3p inhibitor suppressed lung damage in sepsis model mice. In conclusion, miR-19a-3p knockdown could alleviate sepsis-induced lung injury through enhancing USP13 expression. |
| Databáze: | OpenAIRE |
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