G protein-coupled estrogen receptor 1 inhibits the epithelial-mesenchymal transition of goat mammary epithelial cells via NF-κB signaling pathway.

Mastitis is one of the most frequent clinical diseases in dairy animals. Epithelial cells undergoing epithelial-mesenchymal transition (EMT) promote the process of mastitis. Estrogen deficiency is disadvantaged of many tissue inflammation and regeneration, while exogenous estrogen treatment can reverse these effects. G protein-coupled estrogen receptor 1 (GPER1) is a membrane estrogen receptor. However, the potential effects of estrogen via GPER1 on the EMT in goat mammary epithelial cells (GMECs) are still unclear. Here, this study discovered that activation of GPER1 by estrogen could inhibit the EMT in GMECs via NF-κB signaling pathway. Activation of GPER1 by estrogen inhibited the EMT accompanied by upregulation of E-cadherin and downregulation of N-cadherin and vimentin. Meanwhile, mRNA expression of transcription factors including Snail1 and ZEB1 was decreased. Further, like to estrogen, GPER1 agonist G1 repressed the EMT progression. Conversely, GPER1 antagonist G15 reversed all these features induced by estrogen. What's more, GPER1 silencing with shRNA promoted GMECs undergoing EMT. Additionally, estrogen increased the phosphorylation of Erk1/2, which then decreased the phosphorylation and nuclear translocation of NF-κB, inhibiting the NF-κB signaling pathway activity. Taken, GPER1 may act as a suppressor through the regulation of EMT to prevent the development of mastitis.