title: Whey protein concentrate enhances intestinal integrity and influences transforming growth factor-β1 and mitogen-activated protein kinase signalling pathways in piglets after lipopolysaccharide challenge.
abstract: Whey protein concentrate (WPC) has been reported to have protective effects on the intestinal barrier. However, the molecular mechanisms involved are not fully elucidated. Transforming growth factor-β1 (TGF-β1) is an important component in the WPC, but whether TGF-β1 plays a role in these processes is not clear. The aim of this study was to investigate the protective effects of WPC on the intestinal epithelial barrier as well as whether TGF-β1 is involved in these protection processes in a piglet model after lipopolysaccharide (LPS) challenge. In total, eighteen weanling pigs were randomly allocated to one of the following three treatment groups: (1) non-challenged control and control diet; (2) LPS-challenged control and control diet; (3) LPS+5 %WPC diet. After 19 d of feeding with control or 5 %WPC diets, pigs were injected with LPS or saline. At 4 h after injection, pigs were killed to harvest jejunal samples. The results showed that WPC improved (P<0·05) intestinal morphology, as indicated by greater villus height and villus height:crypt depth ratio, and intestinal barrier function, which was reflected by increased transepithelial electrical resistance and decreased mucosal-to-serosal paracellular flux of dextran (4 kDa), compared with the LPS group. Moreover, WPC prevented the LPS-induced decrease (P<0·05) in claudin-1, occludin and zonula occludens-1 expressions in the jejunal mucosae. WPC also attenuated intestinal inflammation, indicated by decreased (P<0·05) mRNA expressions of TNF-α, IL-6, IL-8 and IL-1β. Supplementation with WPC also increased (P<0·05) TGF-β1 protein, phosphorylated-Smad2 expression and Smad4 and Smad7 mRNA expressions and decreased (P<0·05) the ratios of the phosphorylated to total c-jun N-terminal kinase (JNK) and p38 (phospho-JNK:JNK and p-p38:p38), whereas it increased (P<0·05) the ratio of extracellular signal-regulated kinase (ERK) (phospho-ERK:ERK). Collectively, these results suggest that dietary inclusion of WPC attenuates the LPS-induced intestinal injury by improving mucosal barrier function, alleviating intestinal inflammation and influencing TGF-β1 canonical Smad and mitogen-activated protein kinase signalling pathways.
authors.affiliation: The Key Laboratory of Molecular Animal Nutrition,Ministry of Education,Animal Science College,Zhejiang University,Hangzhou 310058,China.
authors.forename: Kan
authors.initials: K
authors.lastname: Xiao
authors.affiliation: The Key Laboratory of Molecular Animal Nutrition,Ministry of Education,Animal Science College,Zhejiang University,Hangzhou 310058,China.
authors.forename: Lefei
authors.initials: L
authors.lastname: Jiao
authors.affiliation: The Key Laboratory of Molecular Animal Nutrition,Ministry of Education,Animal Science College,Zhejiang University,Hangzhou 310058,China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Cao
authors.affiliation: The Key Laboratory of Molecular Animal Nutrition,Ministry of Education,Animal Science College,Zhejiang University,Hangzhou 310058,China.
authors.forename: Zehe
authors.initials: Z
authors.lastname: Song
authors.affiliation: The Key Laboratory of Molecular Animal Nutrition,Ministry of Education,Animal Science College,Zhejiang University,Hangzhou 310058,China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Hu
authors.affiliation: The Key Laboratory of Molecular Animal Nutrition,Ministry of Education,Animal Science College,Zhejiang University,Hangzhou 310058,China.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Han
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D017097:Electric Impedance; D004760:Enterocolitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007422:Intestines / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System; D008297:Male; D009919:Orchiectomy / Q000662:veterinary; D010539:Permeability; D011897:Random Allocation; D034421:Sus scrofa; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D014886:Weaning; D000067816:Whey Proteins / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D062725:Tight Junction Proteins; D053773:Transforming Growth Factor beta1; D000067816:Whey Proteins; C482199:lipopolysaccharide, E coli O55-B5
keywords: EGF epidermal growth factor; ERK extracellular signal-regulated kinase; FD4 fluorescein isothiocyanate dextran 4 kDa; Intestinal integrity; JNK c-jun N-terminal kinase; LF lactoferrin; LPS lipopolysaccharide; MAPK mitogen-activated protein kinase; Mitogen-activated protein kinase; Piglets; TER transepithelial electrical resistance; TGF-β1 transforming growth factor-β1; Transforming growth factor-β1; WPC whey protein concentrate; Whey protein concentrate; ZO-1 zonula occludens-1