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Whey protein concentrate enhances intestinal integrity and influences transforming growth factor-β1 and mitogen-activated protein kinase signalling pathways in piglets after lipopolysaccharide challenge.
Br J Nutr. 2016 Mar 28; 115(6):984-93.BJ

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+Show Affiliations

The Key Laboratory of Molecular Animal Nutrition,Ministry of Education,Animal Science College,Zhejiang University,Hangzhou 310058,China.The Key Laboratory of Molecular Animal Nutrition,Ministry of Education,Animal Science College,Zhejiang University,Hangzhou 310058,China.The Key Laboratory of Molecular Animal Nutrition,Ministry of Education,Animal Science College,Zhejiang University,Hangzhou 310058,China.The Key Laboratory of Molecular Animal Nutrition,Ministry of Education,Animal Science College,Zhejiang University,Hangzhou 310058,China.The Key Laboratory of Molecular Animal Nutrition,Ministry of Education,Animal Science College,Zhejiang University,Hangzhou 310058,China.The Key Laboratory of Molecular Animal Nutrition,Ministry of Education,Animal Science College,Zhejiang University,Hangzhou 310058,China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26810899

Citation

Xiao, Kan, et al. "Whey Protein Concentrate Enhances Intestinal Integrity and Influences Transforming Growth Factor-β1 and Mitogen-activated Protein Kinase Signalling Pathways in Piglets After Lipopolysaccharide Challenge." The British Journal of Nutrition, vol. 115, no. 6, 2016, pp. 984-93.
Xiao K, Jiao L, Cao S, et al. Whey protein concentrate enhances intestinal integrity and influences transforming growth factor-β1 and mitogen-activated protein kinase signalling pathways in piglets after lipopolysaccharide challenge. Br J Nutr. 2016;115(6):984-93.
Xiao, K., Jiao, L., Cao, S., Song, Z., Hu, C., & Han, X. (2016). Whey protein concentrate enhances intestinal integrity and influences transforming growth factor-β1 and mitogen-activated protein kinase signalling pathways in piglets after lipopolysaccharide challenge. The British Journal of Nutrition, 115(6), 984-93. https://doi.org/10.1017/S0007114515005085
Xiao K, et al. Whey Protein Concentrate Enhances Intestinal Integrity and Influences Transforming Growth Factor-β1 and Mitogen-activated Protein Kinase Signalling Pathways in Piglets After Lipopolysaccharide Challenge. Br J Nutr. 2016 Mar 28;115(6):984-93. PubMed PMID: 26810899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Whey protein concentrate enhances intestinal integrity and influences transforming growth factor-β1 and mitogen-activated protein kinase signalling pathways in piglets after lipopolysaccharide challenge. AU - Xiao,Kan, AU - Jiao,Lefei, AU - Cao,Shuting, AU - Song,Zehe, AU - Hu,Caihong, AU - Han,Xinyan, Y1 - 2016/01/26/ PY - 2016/1/27/entrez PY - 2016/1/27/pubmed PY - 2016/7/22/medline KW - EGF epidermal growth factor KW - ERK extracellular signal-regulated kinase KW - FD4 fluorescein isothiocyanate dextran 4 kDa KW - Intestinal integrity KW - JNK c-jun N-terminal kinase KW - LF lactoferrin KW - LPS lipopolysaccharide KW - MAPK mitogen-activated protein kinase KW - Mitogen-activated protein kinase KW - Piglets KW - TER transepithelial electrical resistance KW - TGF-β1 transforming growth factor-β1 KW - Transforming growth factor-β1 KW - WPC whey protein concentrate KW - Whey protein concentrate KW - ZO-1 zonula occludens-1 SP - 984 EP - 93 JF - The British journal of nutrition JO - Br. J. Nutr. VL - 115 IS - 6 N2 - 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. SN - 1475-2662 UR - https://www.unboundmedicine.com/medline/citation/26810899/Whey_protein_concentrate_enhances_intestinal_integrity_and_influences_transforming_growth_factor_β1_and_mitogen_activated_protein_kinase_signalling_pathways_in_piglets_after_lipopolysaccharide_challenge_ L2 - https://www.cambridge.org/core/product/identifier/S0007114515005085/type/journal_article DB - PRIME DP - Unbound Medicine ER -