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A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
Published on: January 27, 2019
MiR-96-5p alleviates inflammatory responses by targeting NAMPT and regulating the NF-κB pathway in neonatal sepsis
Xueli Chen1, Ying Chen1, Li Dai1
1Department of Pediatrics, Maternal and Child Health Hospital of Hubei Province (Women and Children's Hospital of Hubei Province), Wuhan, Hubei, China.
Abstract:
Neonatal septicemia is a serious infectious disease in the neonatal period. MicroRNAs (miRNAs) have been reported to participate in the inflammatory responses in neonatal sepsis. The aim of the present study was to explore the effects and molecular mechanism of miR-96-5p on regulating the inflammatory responses in neonatal sepsis. MiR-96-5p was low expressed while nicotinamide phosphoribosyltransferase (NAMPT) was high expressed in the serum of neonatal septicemia patients. The expression of miR-96-5p was decreased in LPS-induced inflammatory responses. Besides, miR-95-5p relieved LPS-induced inflammatory responses in RAW264.7 cells. NAMPT was demonstrated as a potential target of miR-96-5p, and knockdown of NAMPT reduced inflammatory in RAW264.7 cells stimulated with LPS. Moreover, overexpression of NAMPT reversed the effects of miR-96-5p on LPS-induced inflammatory responses. In addition, miR-96-5p inhibited nuclear factor (NF)-κB signaling pathway in RAW264.7 cells stimulated with LPS. MiR-96-5p alleviated inflammatory responses via targeting NAMPT and inhibiting NF-κB pathway in neonatal sepsis.
Insights
MicroRNA-96-5p (miR-96-5p) combats neonatal septicemia by reducing inflammation. It targets NAMPT and inhibits the NF-κB pathway, offering a potential therapeutic strategy for this serious neonatal infection.
Area of Science:
- Molecular Biology
- Immunology
- Neonatal Medicine
Background:
- Neonatal septicemia is a critical infection in newborns.
- MicroRNAs (miRNAs) play a role in inflammatory responses during sepsis.
- Understanding specific miRNA roles is crucial for therapeutic development.
Purpose of the Study:
- To investigate the role and molecular mechanism of miR-96-5p in regulating inflammatory responses in neonatal sepsis.
- To identify potential molecular targets of miR-96-5p in this context.
Main Methods:
- Analysis of miR-96-5p and NAMPT expression in neonatal septicemia patients.
- In vitro studies using LPS-induced RAW264.7 cells to assess inflammatory responses.
- Luciferase reporter assays and Western blotting to confirm target interaction and pathway inhibition.
- Manipulation of miR-96-5p and NAMPT expression to evaluate their effects on inflammation.
Main Results:
- miR-96-5p was downregulated, while NAMPT was upregulated in neonatal septicemia.
- miR-96-5p suppressed LPS-induced inflammation in RAW264.7 cells.
- NAMPT was identified as a direct target of miR-96-5p.
- miR-96-5p inhibited the NF-κB signaling pathway, and NAMPT overexpression reversed miR-96-5p's anti-inflammatory effects.
Conclusions:
- miR-96-5p exerts anti-inflammatory effects in neonatal sepsis by targeting NAMPT.
- The mechanism involves the inhibition of the NF-κB signaling pathway.
- miR-96-5p represents a potential therapeutic target for neonatal septicemia.
