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TGF-β1 protects intestinal integrity and influences Smads and MAPK signal pathways in IPEC-J2 after TNF-α challenge

The aim of this study was to investigate the protective effects of TGF-β1 on intestinal epithelial barrier, as well as canonical Smad and MAPK signal pathways involved in these protection processes by a IPEC-J2 model stimulated with TNF-α. IPEC-J2 monolayers were treated without or with TNF-α in the...

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Published in:Innate immunity (London, England) England), 2017-04, Vol.23 (3), p.276-284
Main Authors: Xiao, Kan, Cao, Shuting, Jiao, Lefei, Song, Zehe, Lu, Jianjun, Hu, Caihong
Format: Article
Language:English
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Summary:The aim of this study was to investigate the protective effects of TGF-β1 on intestinal epithelial barrier, as well as canonical Smad and MAPK signal pathways involved in these protection processes by a IPEC-J2 model stimulated with TNF-α. IPEC-J2 monolayers were treated without or with TNF-α in the absence or presence of TGF-β1. The results showed that TGF-β1 pretreatment ameliorated TNF-α-induced intestinal epithelial barrier disturbances as indicated by decrease of transepithelial electrical resistance (TER) and increase of paracellular permeability. TGF-β1 also dramatically alleviated TNF-α-induced alteration of TJ proteins ZO-1 and occludin. Moreover, TGF-β1 pretreatment increased TβRII protein expression in IPEC-J2 monolayers challenged with TNF-α. In addition, a significant increase of Smad4 and Smad7 mRNA was also observed in the TGF-β1 pretreatment after TNF-α challenge compared with the control group. Furthermore, TGF-β1 pretreatment enhanced smad2 protein activation. These results indicated that the canonical Smad signaling pathway was activated by TGF-β1 pretreatment. Finally, TGF-β1 pretreatment decreased the ratios of the phosphorylated to total JNK and p38 (p-JNK/JNK and p-p38/p38) and increased the ratio of ERK (p-ERK/ERK). Anti-TGF-β1 Abs reduced these TGF-β1 effects. These results indicated that TGF-β1 protects intestinal integrity and influences Smad and MAPK signal pathways in IPEC-J2 after TNF-α challenge.
ISSN:1753-4259
1753-4267
DOI:10.1177/1753425917690815