State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Int J Mol Sci. 2019 Jan 30;20(3):587. doi: 10.3390/ijms20030587.
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.
乳铁蛋白作为食物中的一种营养活性蛋白，其生物活性已有多项研究，包括抗氧化、抗病毒、抗炎、抗肿瘤、抗菌和抗寄生虫作用，但其保护心血管系统的机制仍不清楚。在本工作中，检测了乳铁蛋白对 HUVECs（人脐静脉内皮细胞）活力的影响，以选择合适的剂量。此外，还进行了转录组学检测和数据分析，以筛选出特殊基因和相关途径。同时，检测了乳铁蛋白对血栓烷 A₂（TXA₂）和前列环素（PGI₂）功能因子的调节作用。然后，将选定基因吡哆醛磷酸酶（PDXP）的小干扰 RNA（siRNA）片段转染到 HUVECs 中，以验证其在保护 HUVECs 功能中的作用。结果表明，乳铁蛋白抑制 TXA2 的表达，激活 PGI₂的表达，以及 PDXP 的激活表达，这显著上调了维生素 B6（VB6）的合成和磷酸肌醇 3-激酶（PI3K）/丝氨酸/苏氨酸蛋白激酶（AKT）/细胞外调节蛋白激酶（ERK）1/2 途径。首次揭示了乳铁蛋白通过激活 PDXP 基因及其相关途径，诱导 VB6 的合成，保护 HUVECs 的功能。
