Exosomal miR-218 regulates the development of endometritis in dairy cows by targeting TGIF2/TGF-β pathway

Abstract

Endometritis affects the reproductive capacity of dairy cows and leads to serious economic losses in dairy farming. Clarification of the pathogenesis of endometritis is necessary to improve the reproductive efficiency of dairy cows. Exosomes and their miRNAs have been proven to play an important role in inflammatory regulation. Exosomal miR-218 is a differentially expressed miRNA found in endometrial epithelial cells (EECs) under endometrial inflammation. Therefore, we investigated the expression of miR-218 in the uterine tissue of dairy cows, lipopolysaccharide (LPS) treated EECs, exosomal vesicles, and regulation of exosomal miR-218 by targeting TGIF-2 inducible factor homology frame 2 (TGIF2)/transforming growth factor-beta (TGF-β). The expression of miR-218 was suppressed in inflammatory uterine tissues and LPS treated EECs. The expression of TGIF2 and TGF-β in inflammatory uterine tissues and LPS treated EECs was significantly higher than those in healthy uterine tissues and EECs (p < 0.01). Interestingly, miR-218 derived from donor cells was found to regulate the expression of the target gene TGIF2 in recipient cells through the fusion of exosomes. Concurrently, the expression of its target gene TGIF2 was also suppressed by miR-218 in donor cells resulting in fewer TGIF2 being transported into recipient cells with exosomal fusion. This may be a novel mechanism of miRNAs-mediated regulation and provides a new reference for analyzing the pathogenesis of endometritis in dairy cows.