1. Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury
- Author
-
You-Lian Chen, Yin-Jing Xie, Zhen-Mi Liu, Wei-Bu Chen, Ru Zhang, Hong-Xing Ye, Wei Wang, Xue-Yan Liu, and Huai-Sheng Chen
- Subjects
Smad Proteins ,RM1-950 ,QD415-436 ,Biochemistry ,Models, Biological ,Mice ,Sepsis ,Fatty Acids, Omega-3 ,Omega-3 fatty acids ,Genetics ,Animals ,Intestinal Mucosa ,Receptor, Notch3 ,Molecular Biology ,Genetics (clinical) ,Smad ,Inflammation ,Gene Expression Profiling ,microRNA-1-3p ,Notch3 ,Disease Management ,Stress oxidative ,Disease Models, Animal ,Intestinal Diseases ,MicroRNAs ,Oxidative Stress ,Gene Expression Regulation ,Intestinal injury ,Molecular Medicine ,Therapeutics. Pharmacology ,Disease Susceptibility ,Biomarkers ,Signal Transduction ,Research Article - Abstract
Background Sepsis is a troublesome syndrome that can cause intestinal injury and even high mortality rates. Omega-3 fatty acids (FAs) are known to protect against intestinal damage. Accordingly, the current study set out to explore if omega-3 FAs could affect sepsis-induced intestinal injury with the involvement of the microRNA (miR)-1-3p/Notch3-Smad axis. Methods First, cecal ligation and perforation (CLP) was performed to establish septic mouse models in C57BL/6J mice, and mouse intestinal epithelial MODE-K cells were induced by lipopolysaccharide (LPS) to establish sepsis cell models. The CLP-induced septic mice or LPS-exposed cells were subjected to treatment with Omega-3 FAs and activin (Smad signaling activator), miR-1-3p inhibitor and over-expressed/short hairpin RNA (oe-/sh)-Notch3 to explore their roles in inflammation, intestinal oxidative stress and cell apoptosis. A dual-luciferase reporter gene assay was further performed to verify the regulatory relationship between miR-1-3p and Notch3. Results Omega-3 FAs inhibited CLP-induced intestinal injury and ameliorated LPS-induced intestinal epithelial cell injury by down-regulating miR-1-3p, as evidenced by decreased levels of tumor necrosis factor-α, interleukin-1β (IL-1β) and IL-6, in addition to diminished levels of reactive oxygen species, malondialdehyde levels and superoxide dismutase activity. Furthermore, miR-1-3p could down-regulate Notch3, which inactivated the Smad pathway. Conclusion Collectively, our findings indicated that omega-3 FAs elevate the expression of Notch3 by down-regulating miR-1-3p, and then blocking the Smad pathway to alleviate intestinal epithelial inflammation and oxidative stress injury caused by sepsis. more...
- Published
- 2022
- Full Text
- View/download PDF