G protein-coupled estrogen receptor 1 inhibits the epithelial-mesenchymal transition of goat mammary epithelial cells via NF-κB signalling 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. Oestrogen deficiency is disadvantaged of many tissue inflammation and regeneration, while exogenous oestrogen treatment can reverse these effects. G protein-coupled estrogen receptor 1 (GPER1) is a membrane estrogen receptor. However, the potential effects of oestrogen via GPER1 on EMT in goat mammary epithelial cells (GMECs) are still unclear. Here, this study discovered that the activation of GPER1 by oestrogen could inhibit the EMT in GMECs via NF-κB signalling pathway. The activation of GPER1 by oestrogen 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 oestrogen, GPER1 agonist G1 repressed the EMT progression. Conversely, GPER1 antagonist G15 reversed all these features induced by oestrogen. What's more, GPER1 silencing with shRNA promoted GMECs undergoing EMT. Additionally, oestrogen increased the phosphorylation of Erk1/2, which then decreased the phosphorylation and nuclear translocation of NF-κB, inhibiting the NF-κB signalling pathway activity. Taken, GPER1 may act as a suppressor through the regulation of EMT to prevent the development of mastitis.