Therapeutic Role of miR-30a in Lipoteichoic Acid-Induced Endometritis via Targeting the MyD88/Nox2/ROS Signaling.
Kangfeng JiangWeiqi YeQian BaiJinyin CaiHaichong WuXiaobing LiPublished in: Oxidative medicine and cellular longevity (2021)
Staphylococcus aureus ( S. aureus ), a notorious pathogenic bacterium prevalent in the environment, causes a wide range of inflammatory diseases such as endometritis. Endometritis is an inflammatory disease in humans and mammals, which prolongs uterine involution and causes great economic losses. MiR-30a plays an importan trole in the process of inflammation; however, the regulatory role of miR-30a in endometritis is still unknown. Here, we first noticed that there was an increased level of miR-30a in uterine samples of cows with endometritis. And then, bovine endometrial epithelial (BEND) cells stimulated with the virulence factor lipoteichoic acid (LTA) from S. aureus were used as an in vitro endometritis model to explore the potential role of miR-30a in the pathogenesis of endometritis. Our data showed that the induction of the miR-30a expression is dependent on NF- κ B activation, and its overexpression significantly decreased the levels of IL-1 β and IL-6. Furthermore, we observed that the overexpression of miR-30a inhibited its translation by binding to 3'-UTR of MyD88 mRNA, thus preventing the activation of Nox2 and NF- κ B and ROS accumulation. Meanwhile, in vivo studies further revealed that upregulation of miR-30a using chemically synthesized agomirs alleviates the inflammatory conditions in an experimental mouse model of endometritis, as indicated by inhibition of ROS and NF- κ B. Taken together, these findings highlight that miR-30a can attenuate LTA-elicited oxidative stress and inflammatory responses through the MyD88/Nox2/ROS/NF- κ B pathway and may aid the future development of novel therapies for inflammatory diseases caused by S. aureus , including endometritis.
Keyphrases
- cell proliferation
- oxidative stress
- long non coding rna
- long noncoding rna
- poor prognosis
- staphylococcus aureus
- pi k akt
- dna damage
- signaling pathway
- reactive oxygen species
- cell death
- induced apoptosis
- mouse model
- immune response
- diabetic rats
- pseudomonas aeruginosa
- drug delivery
- big data
- nuclear factor
- ischemia reperfusion injury
- single cell
- deep learning
- cell cycle arrest
- methicillin resistant staphylococcus aureus
- human health
- heat stress