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β-Casein(94-123)-derived peptides differently modulate production of mucins in intestinal goblet cells

  • Pascale Plaisancié (a1), Rachel Boutrou (a2) (a3), Monique Estienne (a1), Gwénaële Henry (a2) (a3), Julien Jardin (a2) (a3), Armelle Paquet (a1) and Joëlle Léonil (a2) (a3)...
Abstract

We recently reported the identification of a peptide from yoghurts with promising potential for intestinal health: the sequence (94-123) of bovine β-casein. This peptide, composed of 30 amino acid residues, maintains intestinal homoeostasis through production of the secreted mucin MUC2 and of the transmembrane-associated mucin MUC4. Our study aimed to search for the minimal sequence responsible for the biological activity of β-CN(94-123) by using several strategies based on (i) known bioactive peptides encrypted in β-CN(94-123), (ii) in silico prediction of peptides reactivity and (iii) digestion of β-CN(94-123) by enzymes of intestinal brush border membranes. The revealed sequences were tested in vitro on human intestinal mucus-producing HT29-MTX cells. We demonstrated that β-CN(108-113) (an ACE-inhibitory peptide) and β-CN(114-119) (an opioid peptide named neocasomorphin-6) up-regulated MUC4 expression whereas levels of the secreted mucins MUC2 and MUC5AC remained unchanged. The digestion of β-CN(94-123) by intestinal enzymes showed that the peptides β-CN(94-108) and β-CN(117-123) were present throughout 1·5 to 3 h of digestion, respectively. These two peptides raised MUC5AC expression while β-CN(117-123) also induced a decrease in the level of MUC2 mRNA and protein. In addition, this inhibitory effect was reproduced in airway epithelial cells. In conclusion, β-CN(94-123) is a multifunctional molecule but only the sequence of 30 amino acids has a stimulating effect on the production of MUC2, a crucial factor of intestinal protection.

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*For correspondence; e-mail: pascale.plaisancie@inserm.fr
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R Boutrou , J Jardin , A Blais , D Tome & J Leonil 2008 Glycosylations of kappa-casein-derived caseinomacropeptide reduce its accessibility to endo- but not exointestinal brush border membrane peptidases. Journal of Agricultural and Food Chemistry 56 81668173. doi: 10.1021/jf801140d

R Boutrou , C Gaudichon , D Dupont , J Jardin , G Airinei , A Marsset-Baglieri , R Benamouzig , D Tome & J Leonil 2013 Sequential release of milk protein-derived bioactive peptides in the jejunum in healthy humans. American Journal of Clinical Nutrition 97 13141323

ES Corazziari 2009 Intestinal mucus barrier in normal and inflamed colon. Journal of Pediatric Gastroenterology and Nutrition 48(Suppl. 2)S54S55

AP Corfield , N Myerscough , R Longman , P Sylvester , S Arul & M Pignatelli 2000 Mucins and mucosal protection in the gastrointestinal tract: new prospects for mucins in the pathology of gastrointestinal disease. Gut 47 589594

AP Corfield , D Carroll , N Myerscough & CS Probert 2001 Mucins in the gastrointestinal tract in health and disease. Frontiers in Bioscience 6 D1321D1357

M El Homsi , R Ducroc , J Claustre , G Jourdan , A Gertler , M Estienne , A Bado , JY Scoazec & P Plaisancie 2007 Leptin modulates the expression of secreted and membrane-associated mucins in colonic epithelial cells by targeting PKC, PI3K, and MAPK pathways. American Journal of Physiology Gastrointestinal and Liver Physiology 293 G365G373

E Gaudier , A Jarry , HM Blottiere , P de Coppet , MP Buisine , JP Aubert , C Laboisse , C Cherbut & C Hoebler 2004 Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose. American Journal of Physiology Gastrointestinal and Liver Physiology 287 G1168G1174

N Gosalia , SH Leir & A Harris 2013 Coordinate regulation of the gel forming mucin genes at chromosome 11p15.5. Journal of Biological Chemistry 288 67176725

HH Habte , GJ Kotwal , ZE Lotz , MG Tyler , M Abrahams , J Rodriques , D Kahn & AS Mall 2007 Antiviral activity of purified human breast milk mucin. Neonatology 92 96104

HH Habte , C de Beer , ZE Lotz , MG Tyler , D Kahn & AS Mall 2008 Inhibition of human immunodeficiency virus type 1 activity by purified human breast milk mucin (MUC1) in an inhibition assay. Neonatology 93 162170

Y Jinsmaa & M Yoshikawa 1999 Enzymatic release of neocasomorphin and beta-casomorphin from bovine beta-casein. Peptides 20 957962

JD Li , AF Dohrman , M Gallup , S Miyata , JR Gum , YS Kim , JA Nadel , A Prince & CB Basbaum 1997 Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. Proceedings of the National Academy of Sciences of the United States of America 94 967972

B Liu , Z Yu , C Chen , DE Kling & DS Newburg 2012 Human milk mucin 1 and mucin 4 inhibit Salmonella enterica serovar Typhimurium invasion of human intestinal epithelial cells in vitro. Journal of Nutrition 142 15041509

KJ Livak & TD Schmittgen 2001 Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25 402408

D Martinez-Maqueda , B Miralles , S De Pascual-Teresa , I Reveron , R Munoz & I Recio 2012 Food-derived peptides stimulate mucin secretion and gene expression in intestinal cells. Journal of Agricultural and Food Chemistry 60 86008605

T Pelaseyed , JH Bergstrom , JK Gustafsson , A Ermund , GM Birchenough , A Schutte , S van der Post , F Svensson , AM Rodriguez-Pineiro , EE Nystrom , C Wising , ME Johansson & GC Hansson 2014 The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system. Immunological Reviews 260 820

MW Pfaffl , GW Horgan & L Dempfle 2002 Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Research 30 e36

A Philanto-Leppälä , T Rokka & H Korhonen 1998 Angiotensin I converting enzyme inhibitory peptides derived from bovine milk proteins. International Dairy Journal 8 325331

P Plaisancie , J Claustre , M Estienne , G Henry , R Boutrou , A Paquet & J Leonil 2013 A novel bioactive peptide from yoghurts modulates expression of the gel-forming MUC2 mucin as well as population of goblet cells and Paneth cells along the small intestine. Journal of Nutritional Biochemistry 24 213221

S Pugh , AP Jayaraj & KD Bardhan 1996 Duodenal mucosal histology and histochemistry in active, treated and healed duodenal ulcer: correlation with duodenal prostaglandin E2 production. Journal of Gastroenterology and Hepatology 11 120124

MC Rose , FM Piazza , YA Chen , MZ Alimam , MV Bautista , N Letwin & B Rajput 2000 Model systems for investigating mucin gene expression in airway diseases. Journal of Aerosol Medicine 13 245261

N Ruvoen-Clouet , E Mas , S Marionneau , P Guillon , D Lombardo & J Le Pendu 2006 Bile-salt-stimulated lipase and mucins from milk of ‘secretor’ mothers inhibit the binding of Norwalk virus capsids to their carbohydrate ligands. Biochemical Journal 393 627634

V Strugala , PW Dettmar & JP Pearson 2008 Thickness and continuity of the adherent colonic mucus barrier in active and quiescent ulcerative colitis and Crohn's disease. International Journal of Clinical Practice 62 762769

PA Sylvester , N Myerscough , BF Warren , I Carlstedt , AP Corfield , P Durdey & MG Thomas 2001 Differential expression of the chromosome 11 mucin genes in colorectal cancer. Journal of Pathology 195 327335

H Teschemacher 2003 Opioid receptor ligands derived from food proteins. Current Pharmaceutical Design 9 13311344

M Van der Sluis , BA De Koning , AC De Bruijn , A Velcich , JP Meijerink , JB Van Goudoever , HA Buller , J Dekker , I Van Seuningen , IB Renes & AW Einerhand 2006 Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131 117129

A Velcich , W Yang , J Heyer , A Fragale , C Nicholas , S Viani , R Kucherlapati , M Lipkin , K Yang & L Augenlicht 2002 Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 295 17261729

JA Voynow , SJ Gendler & MC Rose 2006 Regulation of mucin genes in chronic inflammatory airway diseases. American Journal of Respiratory Cell and Molecular Biology 34 661665

S Zoghbi , A Trompette , J Claustre , M El Homsi , J Garzon , G Jourdan , JY Scoazec & P Plaisancie 2006 beta-Casomorphin-7 regulates the secretion and expression of gastrointestinal mucins through a mu-opioid pathway. American Journal of Physiology Gastrointestinal and Liver Physiology 290 G1105G1113

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Journal of Dairy Research
  • ISSN: 0022-0299
  • EISSN: 1469-7629
  • URL: /core/journals/journal-of-dairy-research
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