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Biochemical and molecular impacts of lactoferrin on small intestinal growth and development during early life (1) (1) This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.
MedLine Citation:
PMID:  22332905     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 TGF-β1. 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.
Authors:
Yalin Liao; Rulan Jiang; Bo Lönnerdal
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-14
Journal Detail:
Title:  Biochemistry and cell biology = Biochimie et biologie cellulaire     Volume:  -     ISSN:  1208-6002     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8606068     Medline TA:  Biochem Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Nutrition, University of California, Davis, One Shields Ave, Davis, CA 95616, USA.
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