RESUMO
Endometritis and the failure of decidualization of the endometrium are important factors contributing to the increased incidence of abortion. USP22 is associated with various inflammatory diseases and has been shown to be involved in endometrial decidualization in mice. This study aims to investigate whether USP22 is involved in the regulation of inflammatory response and decidualization in human endometrial stromal cells (hESCs). In this study, lipopolysaccharide (LPS) was used to induce inflammation in hESCs, and MPA combined with cAMP was used to induce decidualization of hESCs. USP22 overexpression vector was constructed to study the role of USP22 in endometritis. The results showed that the USP22 protein and mRNA levels were decreased in LPS-induced hESCs. LPS induction increased the levels of TNF-α, IL-1ß, and IL-6, as well as the expression of iNOS and COX2 proteins in hESCs. In the LPS group, the levels of F-actin, PRL, IGFBP1, SLC7A11, and GPX4 proteins decreased, while the levels of lipid peroxidation and total iron content increased. Additionally, the levels of ACSL4 and TFR1 proteins were up-regulated. Overexpression of USP22 reversed LPS-induced cellular inflammation, attenuated decidualization, and inhibited ferroptosis. However, the use of ferroptosis inducers diminished the regulatory effects of USP22 on inflammatory responses and decidualization. In summary, these suggested that USP22 reduces the LPS-induced inflammatory response and regulates the decidualization of hESCs, and possibly involving ferroptosis.
