Lactoferrin Induces the Synthesis of Vitamin B6 and Protects HUVEC Functions by Activating PDXP and the PI3K/AKT/ERK1/2 Pathway.

As a nutritional active protein in foods, multiple studies of the biological activities of lactoferrin had been undertaken, including antioxidant, antiviral, anti-inflammatory, antitumor, antibiosis, and antiparasitic effects, while the mechanism related with its protection of cardiovascular system remained elusive. In the present work, the effect of lactoferrin on the viability of HUVECs (human umbilical vein endothelial cells) was detected to select the proper doses. Moreover, transcriptomics detection and data analysis were performed to screen out the special genes and the related pathways. Meanwhile, the regulation of lactoferrin in the functional factors thromboxane A₂ (TXA₂) and prostacyclin (PGI₂) was detected. Then, the small interfering RNA (SiRNA) fragment of the selected gene pyridoxal phosphatase (PDXP) was transfected into HUVECs to validate its role in protecting HUVECs function. Results showed that lactoferrin inhibited the expression of TXA2 and activated expression of PGI₂, as well as activated expression of PDXP, which significantly up-regulated the synthesis of vitamin B6 (VB6) and the phosphoinositide 3-kinase (PI3K)/ serine/threonine-protein kinase (AKT)/ extracellular regulated protein kinases (ERK) 1/2 pathway. For the first time, we revealed that lactoferrin could induce the synthesis of VB6 and protect HUVECs function through activating PDXP gene and the related pathway.