Tanshinone ⅡA inhibits the lipopolysaccharide-induced epithelial-mesenchymal transition and protects bovine endometrial epithelial cells from pyolysin-induced damage by modulating the NF-κB/Snail2 signaling pathway

• Published in: Theriogenology 2021-12, Vol.176, p.217-224
• Main Authors: Fu, Kaiqiang, Shao, Lingzhen, Mei, Lian, Li, Huatao, Feng, Yanni, Tian, Wenru, Huan, Yanjun, Cao, Rongfeng
• Format: Article
• Language: English
• Subjects: EMT; NF-κB/Snail2; Purulent endometritis; Tanshinone ⅡA
• ISSN: 0093-691X; 1879-3231
• DOI: 10.1016/j.theriogenology.2021.10.001

Mixed infection with Escherichia coli and Trueperella pyogenes (T. pyogenes) leads to purulent endometritis, but the underlying molecular mechanisms remain unclear. The aim of this study was to investigate the effect of tanshinone ⅡA (Tan ⅡA) on E. coli and T. pyogenes -induced purulent endometritis and explore the underlying mechanism. First, lipopolysaccharide (LPS) isolated from E. coli and bacteria-free filtrates (BFFs) isolated from T. pyogenes were used to induce a model of bovine endometrial epithelial cell (bEEC) damage in vitro. bEECs were pretreated with or without Tan ⅡA for 2 h, before LPS and BFFs were introduced to induce damage to investigate the protective effect of Tan IIA. Then, the cytolytic activity and inflammatory response in bEECs were examined using CCK-8, LDH and RT-qPCR assays. Furthermore, we confirmed the molecular mechanism by which Tan ⅡA reversed the damaged phenotypes in LPS- and BFFs-induced bEECs via the NF-κB/Snail2 pathway using qPCR and Western blotting. Tan ⅡA significantly decreased the cytolytic activity and inflammatory response in LPS- and BFFs-induced bEECs. In addition, Tan ⅡA reversed the dysregulation of E-cadherin, N-cadherin and vimentin. Moreover, Tan ⅡA significantly inhibited the activation of the NF-κB signaling pathway and decreased the expression level of Snail2, which is the main regulator of the epithelial-mesenchymal transition (EMT). In summary, Tan ⅡA inhibits the LPS-induced EMT and protects bEECs from pyolysin-induced damage by modulating the NF-κB/Snail2 signaling pathway. •Tan ⅡA significantly decreased the cytolytic activity and the inflammatory response in bEECs induced by LPS and BFF.•Tan ⅡA reversed the LPS-induced downregulation of E-cadherin and upregulations of N-cadherin and vimentin.•Tan ⅡA repressed the migration of bEECs and the expression of inflammatory cytokines induced by LPS.•Tan ⅡA significantly inhibited the activation of NF-κB signaling pathway, and decreased the expression level of snail2.