Jiang Rulan, Lönnerdal Bo
Department of Nutrition, University of California, Davis, CA, 95616, USA.
Biometals. 2014 Oct;27(5):831-41. doi: 10.1007/s10534-014-9746-3. Epub 2014 May 16.
Lactoferrin (Lf) is an iron-binding glycoprotein present in high concentration in human milk. It is a pleiotropic protein and involved in diverse bioactivities, such as stimulation of cell proliferation and immunomodulatory activities. Lf is partly resistant to proteolysis in the gastrointestinal tract. Thus, Lf may play important roles in intestinal development. Due to differences in amino acid sequences and isolation methods, Lfs from human and bovine milk as well as commercially available bovine Lf (CbLf) may differ functionally or exert their functions via various mechanisms. To provide a potential basis for further applications of CbLf, we compared effects of Lfs on intestinal transcriptomic profiling using an intestinal epithelial cell model, human intestinal epithelial crypt-like cells (HIEC). All Lfs significantly stimulated proliferation of HIEC and no significant differences were found among these three proteins. Microarray assays were used to investigate transcriptomic profiling of intestinal epithelial cells in response to Lfs. Selected genes were verified by RT-PCR with a high validation rate. Genes significantly regulated by hLf, bLf, and CbLf were 150, 395 and 453, respectively. Fifty-four genes were significantly regulated by both hLf and CbLf, whereas 129 genes were significantly modulated by bLf and CbLf. Although only a limited number of genes were regulated by all Lfs, the three Lfs positively influenced cellular development and immune functions based on pathway analysis using IPA (Ingenuity). Lfs stimulate cellular and intestinal development and immune functions via various signaling pathways, such as Wnt/β-catenin signaling, interferon signaling and IL-8 signaling.
乳铁蛋白（Lf）是一种在人乳中高浓度存在的铁结合糖蛋白。它是一种多效性蛋白质，参与多种生物活性，如刺激细胞增殖和免疫调节活性。Lf在胃肠道中对蛋白水解有一定抗性。因此，Lf可能在肠道发育中发挥重要作用。由于氨基酸序列和分离方法的差异，人乳和牛乳中的Lf以及市售的牛Lf（CbLf）在功能上可能有所不同，或者通过各种机制发挥其功能。为了为CbLf的进一步应用提供潜在依据，我们使用肠道上皮细胞模型——人肠道上皮隐窝样细胞（HIEC）比较了不同Lf对肠道转录组谱的影响。所有Lf均显著刺激HIEC的增殖，且这三种蛋白之间未发现显著差异。使用微阵列分析来研究肠道上皮细胞对Lf的转录组谱。选定的基因通过RT-PCR进行验证，验证率很高。受hLf、bLf和CbLf显著调控的基因分别为150个、395个和453个。有54个基因受hLf和CbLf共同显著调控，而有129个基因受bLf和CbLf显著调控。尽管所有Lf共同调控的基因数量有限，但基于使用IPA（英智）的通路分析，这三种Lf对细胞发育和免疫功能有积极影响。Lf通过各种信号通路刺激细胞和肠道发育以及免疫功能，如Wnt/β-连环蛋白信号通路、干扰素信号通路和IL-8信号通路。
