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Published on: May 2, 2018
Methylprednisolone Attenuates Lipopolysaccharide-Induced Sepsis by Modulating the Small Nucleolar RNA Host Gene
Li Zhang1, Wei Tan1, Xinmiao Song1
1Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Abstract:
Sepsis has become a major public health problem worldwide. Methylprednisolone sodium succinate (MP) is a commonly used drug to prevent inflammation. However, the role and underlying mechanism of MP in sepsis remain vague. MP inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-17 and suppressed cell growth in alveolar type II epithelial cells (ATII cells). Small nucleolar RNA host gene 5 (SNHG5) expression was inhibited by LPS and restored by MP. Upregulation of SNHG5 inhibited the cellular role of LPS in ATII cells, and further, downregulation of SNHG5 inhibited the cellular role of MP in ATII cells under LPS conditions. SNHG5 elevated the expression of Copine 1 (CPNE1) by enhancing the mRNA stability of CPNE1. Increasing CPNE1 expression restored the silenced SNHG5-induced inhibitor role of MP in ATII cells under LPS conditions. Finally, MP attenuated lung injury and TNF-α and IL-17 secretion in an LPS-induced sepsis mouse model. Overall, this study investigated the mechanism underlying the effect of MP treatment in sepsis and, for the first time, revealed the important role of the SNHG5/CPNE1 pathway in the development and treatment of sepsis and the potential to serve as a diagnostic and therapeutic target for sepsis.
Insights
Methylprednisolone succinate (MP) treats sepsis by regulating the SNHG5/CPNE1 pathway. This study reveals MP
Area of Science:
- Biomedical Research
- Molecular Biology
- Immunology
Background:
- Sepsis is a critical global health issue.
- Methylprednisolone sodium succinate (MP) is used to manage inflammation.
- The precise mechanism of MP in sepsis requires elucidation.
Purpose of the Study:
- To investigate the mechanism of MP in sepsis.
- To explore the role of SNHG5 and CPNE1 in MP's action.
- To identify potential diagnostic and therapeutic targets for sepsis.
Main Methods:
- In vitro studies using alveolar type II epithelial cells (ATII cells) exposed to lipopolysaccharide (LPS).
- Analysis of gene expression (SNHG5, CPNE1) and protein levels (TNF-α, IL-17).
- In vivo studies using an LPS-induced sepsis mouse model.
Main Results:
- MP inhibited LPS-induced TNF-α and IL-17 production and suppressed cell growth in ATII cells.
- MP restored LPS-induced downregulation of SNHG5 expression.
- The SNHG5/CPNE1 pathway was identified as crucial for MP's therapeutic effect in sepsis.
Conclusions:
- MP exerts its anti-sepsis effects through the SNHG5/CPNE1 pathway.
- SNHG5 enhances CPNE1 expression by stabilizing its mRNA.
- The SNHG5/CPNE1 pathway represents a potential therapeutic target for sepsis treatment.
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