UFM1 inhibits the activation of the pyroptosis in LPS-induced goat endometritis.

Infertility, abortion, and stillbirth caused by endometritis are the main factors affecting fertility in ruminants. Lipopolysaccharide (LPS)-mediated inflammation is the main cause of endometritis. Toll-like receptor 4 (TLR4) pathway and pyroptosis play an important role in the inflammation, but the underlying mechanism is still unclear. Previous studies have reported that UFMylation, a ubiquitin-like post-translational modifier, plays an important regulatory role in inflammation via the TLR4 pathway; however, its relationship with pyroptosis is still unclear. Our result showed that LPS induced inflammation by activating the TLR4 pathway and pyroptosis in goat endometrial epithelial cells (gEECs). We also found that TAK-242,a specific inhibitor of the TLR4 pathway, inhibited the pyroptosis pathway. In addition, with an increased LPS treatment time, ubiquitin-folding modifier factor 1 (UFM1) conjugated proteins were highly expressed in gEECs. Moreover, overexpression of UFM1 inhibited LPS-induced activation of the TLR4 pathway and pyroptosis, whereas si-UFM1 produced contrasting results. After inhibiting the TLR4 pathway, si-UFM1 could not upregulate the expression of nod-like receptor family protein 3 (NLRP3), cleavage caspase-1, or cleavage gasdermin D (GSDMD). In conclusion, these results suggest that UFM1 inhibits pyroptosis activation in LPS-induced gEECs through the TLR4 pathway.