4-Phenylbutyric acid accelerates rehabilitation of barrier function in IPEC-J2 cell monolayer model |
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| Institution: | Animal Nutritional Genome and Germplasm Innovation Research Center,College of Animal Science and Technology,Hunan Agricultural University,Changsha,Hunan 410128,China;Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs,Feed Research Institute,Chinese Academy of Agricultural Sciences,Beijing 100081,China;Animal Nutritional Genome and Germplasm Innovation Research Center,College of Animal Science and Technology,Hunan Agricultural University,Changsha,Hunan 410128,China;Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs,Feed Research Institute,Chinese Academy of Agricultural Sciences,Beijing 100081,China;Animal Nutritional Genome and Germplasm Innovation Research Center,College of Animal Science and Technology,Hunan Agricultural University,Changsha,Hunan 410128,China;Laboratory of Animal Nutritional Physiology and Metabolic Process,Institute of Subtropical Agriculture,Chinese Academy of Sciences,Changsha,Hunan 410125,China |
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| Abstract: | As the first line of defence against pathogens and endotoxins crossing the intestine-blood barrier, the intestinal epithelial barrier plays a determinant role in pigs' health and growth. 4-Phenylbutyric acid (4-PBA), an aromatic fatty acid, was reported to benefit homeostasis of endoplasmic reticulum and protein synthesis. However, whether 4-PBA affects intestinal epithelial barrier function in pigs is unknown. This study aimed to explore the effects of 4-PBA on the intestinal barrier function, using in vitro models of well-differentiated intestinal porcine epithelial cell (IPEC-J2) monolayers in the transwell plates. Cell monolayers with or without 4-PBA (1.0 mmol/L) treatment were challenged with physical scratch, deoxynivalenol (DON, 2.0 μg/mL, 48 h), and lipopolysaccharide (LPS, 5.0 μg/mL, 48 h), respectively. Transepithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran (FD-4) permeability were measured to indicate barrier integrity and permeability. Real-time PCR and Western blot were conducted to determine relative gene and protein expressions of tight junction proteins. As expected, physical scratch, DON, and LPS challenges decreased TEER and increased FD-4 permeability. 4-PBA treatment accelerated cell mitigation and rehabilitation of the physical scratch-damaged intestinal epithelial barrier but did not alleviate DON or LPS induced barrier damage. However, once 48-h DON and LPS challenges were removed, rehabilitation of the epithelial barrier function of IPEC-J2 monolayer was accelerated by the 4-PBA treatment. Also, the relative gene and protein expressions of zonula occludens-1 (ZO-1), occludin, and claudin-1 were further upregulated by the 4-PBA treatment during the barrier rehabilitation. Taken together, 4-PBA accelerated the IPEC-J2 cell monolayer barrier recovering from physical scratch, DON-, and LPS-induced damage, via enhancing cell mitigation and expressions of tight junction proteins. |
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| Keywords: | 4-Phenylbutyric acid Intestinal barrier Tight junction Intestinal porcine epithelial cell Deoxynivalenol Lipopolysaccharide |
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