MicroRNA miR-24-3p Mediates the Negative Regulation of Lipopolysaccharide-Induced Endometrial Inflammatory Response by Targeting TNF Receptor-Associated Factor 6 (TRAF6)

Abstract

Purpose Endometritis is a female reproductive disease that affects the cattle industries development and microRNAs (miRNAs) play a pivotal role and critical regulators of the innate immune response in varieties of diseases. The present study intends to investigate the regulatory role of miR‐24-3p in the innate immune response involved in endometritis and evaluate its therapeutic potential. Methods Whole mice uteri and bovine endometrial epithelial cells (BEECs) were separately stimulated with LPS. The BEECs were also transfected with miR-24-3p mimic and negative control; si TRAF6 and siNC; pcDNA3.1 empty and pcDNA3.1(+) TRAF6 separately with LPS stimulation. The expression levels of miR‐24-3p and TRAF6 were measured via quantitative real‐time polymerase chain reaction (qRT-PCR) and Western blot, respectively. LPS‐induced inflammatory response assessed by inflammatory cytokines secretion and expression via ELISA and qRT-PCR. Bioinformatics analysis and luciferase reporter assay validated the interaction between miR‐24-3p and TRAF6 . The activation of the NF‐ĸB/MAPK pathway and p65 phosphorylation was investigated by Western blot and immunofluorescence assay, respectively. Results The expression of miR‐24-3p was decreased, and TRAF6 was elevated with an increased level of pro-inflammatory cytokines in LPS‐treated BEECs and mice uterus. The overexpression of miR‐24-3p suppressed LPS‐induced secretion of inflammatory cytokines (IL‐1β, IL‐6, IL-8 and TNF-α) and deactivation of NF‐ĸB/MAPK pathways. The downregulation of TRAF6 inhibited LPS‐induced inflammatory response in BEECs. TRAF6 is validated as a target of miR‐24-3p, and miR‐24-3p reversed the overexpression of cloned TRAF6 on inflammation response in BEECs. Conclusion Our findings demonstrate that the overexpression of miR‐24-3p attenuates endometrial inflammation and the expression of pro-inflammatory mediators via suppressing TRAF6 . Therefore, modulating the pathogenesis of endometritis and possibly, a therapeutic potential against endometritis.

Tetrahydrocannabivarin (THCV) Protects Adipose-Derived Mesenchymal Stem Cells (ASC) against Endoplasmic Reticulum Stress Development and Reduces Inflammation during Adipogenesis

“…Similarly, we observed that the overexpression of miR-203b has a beneficial effect on metabolic homeostasis [ 39 ]. We have also found an increase in the expression of miR-21, miR-24-3p and miR-146-5p, which are involved in the activation of a pro-inflammatory macrophage phenotype and the attenuation of inflammation [ 40 , 41 , 42 ].…”

Differential Expression of ATM, NF-KB, PINK1 and Foxo3a in Radiation-Induced Basal Cell Carcinoma

“…Furthermore, miR-24 expression decreases with cellular senescence [ 83 ], and it was defined as a mitochondrial miR (mitomiR) [ 84 ]. It was described that miR-24-3p and miR-124 attenuate the expression of pro-inflammatory mediators via NF-kB signaling [ 85 , 86 ]. miR-124 also increases in senescent skin, while it decreases during tumorigenesis, particularly in squamous cell carcinoma [ 87 ].…”

SHED-derived exosomes attenuate trigeminal neuralgia after CCI of the infraorbital nerve in mice via the miR-24-3p/IL-1R1/p-p38 MAPK pathway

“…It has been observed that Exo-derived miR-24-3p promotes M2 macrophage polarization [56,57]. Interestingly, previous studies have established that miR-24-3p plays a role in promoting in ammation recovery [58][59][60][61]. However, the speci c mechanisms by which miR-24-3p affects microglia and its potential contribution to pain relief remain largely unknown.…”