Biochemical and molecular impacts of lactoferrin on small intestinal growth and development during early life
Date
2012
Authors
Liao, Yalin
Jiang, R.
Lonnerdal, Bo
Journal Title
Journal ISSN
Volume Title
Publisher
National Research Council of Canada
Abstract
Postnatal modeling of the intestinal epithelium has long-term impacts on the healthy development of infants and relies largely on nutrient composition of the diet. Lactoferrin (Lf) is among the various human milk trophic factors that facilitate the infant intestinal adaptation. Hydrolysis of Lf is minimal at the prevailing postprandial pH of infants, and Lf may therefore have greater biological potential in infants than in adults. Lf bidirectionally stimulates concentration-dependent proliferation and differentiation of small intestinal epithelial cells, and therefore affects small intestinal mass, length, and epithelial digestive enzyme expression. A 105 kDa Lf receptor (LfR) specifically mediates the uptake of Lf into enterocytes and crypt cells. Mechanistically, the complex of Lf and LfR is internalized through clathrin-mediated endocytosis; both iron-free apo-Lf and iron-saturated holo-Lf activate the PI3K/Akt pathway, whereas only apo-Lf triggers ERK1/2 signaling. Lf enters the nucleus, where it can stimulate thymidine incorporation into crypt cells, regulating transcription of genes such as TGFb1. In the fetus, the plasma membrane LfR is at the highest abundance in the small intestine, and the receptor gene is tightly controlled at multiple levels. Aspecific microRNA, miR-584, is involved in the posttranscriptional regulation of LfR, and in the human LfR DNA promoter, 2 Sp1 binding sites have been characterized functionally. Finally, cell proliferation and global gene expression reveal that native bovine Lf can perform biological activities similar to those exerted by human Lf in postnatal small intestinal development.
Description
Keywords
Keywords: Biological potential; Concentration-dependent; Crypt cells; Development; Digestive enzymes; Early life; Enterocytes; Growth and development; Human milk; Intestinal development; Intestinal epithelial cells; Intestinal epithelium; Lactoferrin; MicroRNAs; Mu Development; Lactoferrin; Lactoferrin receptor; Small intestine
Citation
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Source
Biochemistry and Cell Biology
Type
Journal article