title: Effects of lactoferrin on intestinal epithelial cell growth and differentiation: an in vivo and in vitro study.
abstract: This study was designed to analyse the effects of human (h) and bovine lactoferrin (bLF) on the growth and differentiation of intestinal cells using the mice model supplemented with Lactoferrin (LF) and the enterocyte-like model of Caco-2 cells which spontaneously differentiate after confluency. In mice, bLF supplementation increased jejunal villus height and the expression of several intestinal brush border membrane enzymes activities. Addition of bLF or hLF to undifferentiated Caco-2 cells was able to increase cell proliferation with confluency being reached more rapidly. Moreover, when Caco-2 cells were grown in the presence of LF for 3 weeks, brush-border membrane-associated enzyme activities i.e. sucrase, alkaline phosphatase and neutral aminopeptidase, as well as the L-glutamate transporter expression were all increased indicating an increased Caco-2 cell differentiation. Accordingly, cDNA Atlas array and Western blot analysis of cell cycle proteins shown a decreased expression of Cdck2 and an increased TAF1 expression; these proteins being implicated in the regulation of numerous genes related to cellular proliferation and differentiation. These modifications were associated with an inhibition of Caco-2 cell spontaneous apoptosis. Altogether, our results indicate that LF increase in vivo and in vitro enterocyte differentiation. In addition, LF was found to increase in vitro enterocyte proliferation resulting in higher cell density in cell flasks, an effect that was likely partly due to a reduction of the cellular apoptosis. The different stimulation patterns observed for the different parameters associated with cell differentiation in relationship with specific gene regulation is discussed.
authors.affiliation: UMR 914 INRA- AgroParisTech Nutrition Physiology and Ingestive Behaviour, 16 rue Claude Bernard, 75005, Paris, France, blais@agroparistech.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Blais
authors.forename: Cuibai
authors.initials: C
authors.lastname: Fan
authors.forename: Thierry
authors.initials: T
authors.lastname: Voisin
authors.forename: Najat
authors.initials: N
authors.lastname: Aattouri
authors.forename: Michel
authors.initials: M
authors.lastname: Dubarry
authors.forename: François
authors.initials: F
authors.lastname: Blachier
authors.forename: Daniel
authors.initials: D
authors.lastname: Tomé
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D018826:CD13 Antigens / Q000378:metabolism; D018938:Caco-2 Cells; D002417:Cattle; D002454:Cell Differentiation; D049109:Cell Proliferation; D020895:Enterocytes / Q000166:cytology / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000502:physiology; D007781:Lactoferrin / Q000008:administration & dosage / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013394:Sucrase-Isomaltase Complex / Q000378:metabolism
chemical_list: C490098:LTF protein, human; D000469:Alkaline Phosphatase; D013394:Sucrase-Isomaltase Complex; D018826:CD13 Antigens; D007781:Lactoferrin