Therapeutic Role of miR-30a in Lipoteichoic Acid-Induced Endometritis via Targeting the MyD88/Nox2/ROS Signaling.

Kangfeng Jiang,Xiaobing Li,Qian Bai,Weiqi Ye,Jinyin Cai,Haichong Wu,Laura Bravo

doi:10.1155/2021/5042048

Abstract

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-κB activation, and its overexpression significantly decreased the levels of IL-1β 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-κB 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-κB. Taken together, these findings highlight that miR-30a can attenuate LTA-elicited oxidative stress and inflammatory responses through the MyD88/Nox2/ROS/NF-κB pathway and may aid the future development of novel therapies for inflammatory diseases caused by S. aureus, including endometritis.

Highlights

Endometritis is a reproductive disorder characterized by local inflammation of the endometrium, which leads to delayed uterine involution and huge economic losses [1,2,3].Gram-positive bacteria Staphylococcus aureus (S. aureus) has been recognized as a typical opportunistic pathogen prevalent in the environment, which has the potential to induce endometritis [4]
These findings highlight that miR30a can attenuate Lipoteichoic acid (LTA)-elicited oxidative stress and inflammatory responses through the MyD88/NADPH oxidase2 (Nox2)/reactive oxygen species (ROS)/NF-κB pathway and may aid the future development of novel therapies for inflammatory diseases caused by S. aureus, including endometritis
Enzyme-Linked Immunosorbent Assay (ELISA) results showed that these proinflammatory cytokines were remarkably increased in the endometritis group (Figure 1(b))

Summary

Introduction

Endometritis is a reproductive disorder characterized by local inflammation of the endometrium, which leads to delayed uterine involution and huge economic losses [1,2,3].Gram-positive bacteria Staphylococcus aureus (S. aureus) has been recognized as a typical opportunistic pathogen prevalent in the environment, which has the potential to induce endometritis [4]. Lipoteichoic acid (LTA), a negatively charged glycolipid, exists on the cell wall surface of S. aureus [6]. Emerging evidence has shown that LTA has the same proinflammatory properties as lipopolysaccharide (LPS) and plays a crucial role in the inflammatory reactions induced by S. aureus [7, 8]. Endometrial epithelial cells express toll-like receptors (TLRs) and participate in the pathogenesis of endometritis [9]. TLRs recognize pathogen-associated molecular patterns (PAMPs) of pathogenic bacteria and trigger inflammatory responses via intracellular signaling cascade, in which MyD88 is an important adaptor protein [10, 11]. A recent report using purified LTA from S. aureus has clearly indicated that S. aureus LTA can efficiently stimulate monocytes through TLR2to secrete inflammatory mediators [12]

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Results

Conclusion