Transcriptomic profiling of intestinal epithelial cells in response to human, bovine and commercial bovine lactoferrins (623.2)

Abstract

Lactoferrin (Lf) is an iron‐binding protein abundantly present in human milk. It is multifunctional and comparatively resistant to gastrointestinal proteolysis. Thus, Lf may play critical roles in intestinal development. Due to differences in sequences and isolation methods, Lfs from human and bovine milk as well as commercial available bovine Lf (CbLf) may differ functionally or exert functions diversely. The objective of the present study was to examine and compare effects of CbLf and Lfs isolated from human and bovine milk on intestinal epithelial cells and thus to provide a basis for applications of CbLf. Normal crypt‐like human intestinal epithelial crypt cells (HIEC) were used to evaluate effects of Lfs on intestinal cell proliferation and transcriptomic profiling. All Lfs (4‐50 µg/mL) significantly stimulated proliferation of HIEC and no differences were found among Lfs. Microarray assays (Illumina) were then conducted to investigate transcriptomic profiling of HIEC in response to Lfs. Genes markedly (>1.5 or < 0.5 fold) regulated by hLf, bLf, and CbLf were 152, 367, and 455, respectively. Although only few genes (16) were regulated by all Lfs, they remarkably stimulate signaling pathways tightly related to cellular development based on pathway analysis by IPA (Ingenuity). All Lfs triggered various signaling pathways, such as growth hormone signaling, cell cycle: G1/S checkpoint regulation, and IGF‐1 signaling. In summary, all Lfs may play important roles in intestinal development but through various mechanisms.