Regulatory Effect Of Umbilical Cord Mesenchymal Stem Cells On Bovine Mammary Epithelial Cells Physiological Function Mediated By PI3K/AKT/mTOR Signaling Pathway

Based on our previous research, bovine mammary epithelial cells (BMECs) model was adapted for the investigation on regulatory effect of umbilical cord mesenchymal stem cells (UC-MSCs) on the proliferation, apoptosis, cell cycle and lactation function of bovine mammary epithelial cells mediated by PI3K/AKT/mTOR signaling pathway. PI3K inhibitor LY294002 and mTOR inhibitor rapamycin (RAPA) were used to block the key signaling molecules. This research is expected to provide the mechanism of UC-MSCs promoting BMECs proliferation, inhibiting BMECs apoptosis and regulating cell cycle, besides more specific laboratory basis for the mechanism for enhancing secretion of BMECs.Results indicated that co-cultivation of UC-MSCs and BMECs had significantly promote proliferation of BMECs and inhibit BMECs apoptosis, cell cycle of BMECs was affected and lactation function of BMECs was elevated, expression levels of mRNA of signaling molecules in PI3K/AKT/mTOR pathway were altered. PI3K inhibitor LY294002 and mTOR inhibitor rapamycin inhibited proliferation of BMECs, promoted apoptosis of BMECs, cell cycle of BMECs was altered and secretionfability of BMECs was weakened. Expression of signaling molecules in PI3K/AKT/mT0R pathway was down-regulated, whereas co-cultivation with UC-MSCs had attenuated this trend significantly.The following opinions can be concluded from the current research:① Co-culturing UC-MSCs and BMECs (in ratio of 1:2) can promote BMEcs proliferation and inhibit BMECs apoptosis, impact the cell cycle, enhance the secretion ability of BMECs and up-regulate the expression of GLUT 1② PI3K/AKT/mTOR pathway is involved in regulating the proliferation, apoptosis, cell cycle, secretion ability and GLUT1 expression of BMECs.③ PI3K/AKT/mTOR pathway blockers, like LY294002 and RAPA, can inhibit BMECs proliferation, promote apoptosis of BMECs, regulate the cell cycle, inhibit the secretion ability of BMECs, and down-regulate the expression of GLUT 1.④ Expression of signaling molecules in PI3K/AKT/mTOR pathway can be inhibited by the inhibitors, LY294002 and RAPA.⑤ UC-MSCs can reactivate the PI3K/AKT/mTOR pathway blocked by inhibitors and recover its regulatory functions on BMECs⑥ Regulatory effect of UC-MSCs on cell proliferation, apoptosis, cell cycle, secretion and GLUT1 expression of BMECs is activated by the PI3K/AKT/mTOR pathway.