Enforced expression of miR-92b blunts E. coli lipopolysaccharide-mediated inflammatory injury by activating the PI3K/AKT/β-catenin pathway via targeting PTEN

Abstract

Endometritis is a reproductive disorder characterized by an inflammatory response in the endometrium, which causes significant economic losses to the dairy farming industry. MicroRNAs (miRNAs) are implicated in the inflammatory response and immune regulation following infection by pathogenic bacteria. Recent miRNA microarray analysis showed an altered expression of miR-92b in cows with endometritis. In the present study, we set out to investigate the regulatory mechanism of miR-92b in endometritis. Here, qPCR results first validated that miR-92b was down-regulated during endometritis. And then, bovine endometrial epithelial cells (BEND cells) stimulated by high concentration of lipopolysaccharide (LPS) were employed as an in vitro inflammatory injury model. Our data showed that overexpression of miR-92b significantly suppressed the activation of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF‐κB) in LPS-stimulated BEND cells, thereby reducing pro-inflammatory cytokines release and inhibiting cell apoptosis. Looking into the molecular mechanisms of regulation of inflammatory injury by miR-92b, we observed that overexpression of miR-92b restrained TLR4/NF‐κB by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT)/β-catenin pathway. Furthermore, the luciferase reporter assay suggested that miR-92b targeted inhibition of phosphatase and tensin homolog (PTEN), an inhibitor of the PI3K/AKT/β-catenin pathway. Importantly, in vivo experiments confirmed that up-regulation of miR-92b attenuated the pathological injury in an experimental murine model of LPS-induced endometritis. Collectively, these findings show that enforced expression of miR-92b alleviates LPS-induced inflammatory injury by activating the PI3K/AKT/β-catenin pathway via targeting PTEN, suggesting a potential application for miR-92b-based therapy to treat endometritis or other inflammatory diseases.

Astragalus polysaccharides and astragaloside IV alleviate inflammation in bovine mammary epithelial cells by regulating Wnt/β-catenin signaling pathway

“…In this study, we experimentally demonstrated that β-catenin in Wnt signaling negatively regulated the expression of inflammation and oxidative stress factors in LPS-treated BMECs, similar to the findings by Jiang et al [ 10 , 40 , 41 ]. In experiments of bovine endometrial epithelial cells stimulated with LPS, LPS was reported to inhibit the intracellular expression of β-catenin and promote inflammatory cell damage [ 40 ].…”

“…In this study, we experimentally demonstrated that β-catenin in Wnt signaling negatively regulated the expression of inflammation and oxidative stress factors in LPS-treated BMECs, similar to the findings by Jiang et al [ 10 , 40 , 41 ]. In experiments of bovine endometrial epithelial cells stimulated with LPS, LPS was reported to inhibit the intracellular expression of β-catenin and promote inflammatory cell damage [ 40 ]. Moreover, β-catenin was found to negatively regulate the inflammatory response induced by Salmonella typhimurium , and stimulation of mouse models and colonic epithelial cells by this strain aided the degradation of β-catenin and increased the expression of IL-6 and TNF-α [ 10 ].…”

miRNA expression profiles of peripheral white blood cells from beef heifers with varying reproductive potential

“…Expression of miR-92b was significantly upregulated in the porcine placenta on day 90 of gestation ( Su et al, 2010 ). In a study reported in cattle, miR-92b (downregulated expression) was associated with endometritis, an inflammatory response in the endometrium that causes reproductive disorder ( Jiang et al, 2021 ). The authors further reported that over-expression of miR-92b significantly suppressed the activation of the toll-like receptor in lipopolysaccharide-mediated bovine endometrial cells, thereby reducing pro-inflammatory cytokines and inhibiting cell apoptosis ( Jiang et al, 2021 ).…”

Berberine enhances autophagic flux by activating the Nrf2 signaling pathway in bovine endometrial epithelial cells to resist LPS‐induced apoptosis

“…The endometrium, the first tissue layer exposed to bacteria, plays a vital role in protecting the uterus (Umar et al, 2021). An intact and healthy endometrium protects the uterus from bacteria (Jiang et al, 2021). However, recent studies have demonstrated that LPS damages the intact endometrium by inducing apoptosis in endometrial epithelial cells (Chen et al, 2021; Gao et al, 2021).…”