期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 235, 期 5, 页码 4766-4777出版社
WILEY
DOI: 10.1002/jcp.29354
关键词
AKT; NF-kappa B; endometritis; lipopolysaccharide; miR-488; ROS
资金
- National Natural Science Foundation of China [31772816]
Endometritis is an inflammatory change in the structure of the endometrium due to various causes and is a common cause of infertility. Studies have confirmed that microRNAs (miRNAs) play a key regulatory role in various inflammatory diseases. However, the miRNA-mediated mechanism of endometrial inflammation induced by lipopolysaccharides (LPS) remains unclear. In this study, real-time quantitative polymerase chain reaction, Western blot analysis, immunofluorescence and Rac family small GTPase 1 (Rac1) interference were used to reveal the overexpression of miR-488 in the LPS-induced bovine uterus, and the effect of protein kinase B kappa-light chain enhancement of the nuclear factor-activated B cells (AKT/NF-kappa B) pathway in intimal epithelial cells. The results showed that the expression of inflammatory cytokines such as interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha in the experimental group was significantly lower than that in the control group when miR-488 was overexpressed. Similar results were observed in the expression levels of p-AKT, p-IKK, and p-p65 proteins. In addition, the dual-luciferase reporter system confirmed that miRNA-488 may directly target the 3 '-untranslated region of Rac1. In turn, the expression of Rac1 was inhibited. Moreover, the nuclear translocation of NF-kappa B was inhibited, and meanwhile, the accumulation of reactive oxygen species (ROS) in the cells was reduced. Thus, we provide basic data for the negative regulation of miR-488 in LPS-induced inflammation by inhibiting ROS production and the AKT/NF-kB pathway in intimal epithelial cells.
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