| Autor: |
Zhang, Xu‐Yu, Liu, Zi‐Meng, Zhang, Hu‐Fei, Li, Yun‐Sheng, Wen, Shi‐Hong, Shen, Jian‐Tong, Huang, Wen‐Qi, Liu, Ke‐Xuan |
| Předmět: |
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| Zdroj: |
Journal of Cellular & Molecular Medicine; Jun2016, Vol. 20 Issue 6, p1014-1023, 10p |
| Abstrakt: |
Intestinal ischaemia/reperfusion (I/R) severely disrupts gut barriers and leads to high mortality in the critical care setting. Transforming growth factor ( TGF)-β1 plays a pivotal role in intestinal cellular and immune regulation. However, the effects of TGF-β1 on intestinal I/R injury remain unclear. Thus, we aimed to investigate the effects of TGF-β1 on gut barriers after intestinal I/R and the molecular mechanisms. Intestinal I/R model was produced in mice by clamping the superior mesenteric artery for 1 hr followed by reperfusion. Recombinant TGF-β1 was intravenously infused at 15 min. before ischaemia. The results showed that within 2 hrs after reperfusion, intestinal I/R disturbed intestinal immunoglobulin A class switch recombination (IgA CSR), the key process of mucosal IgA synthesis, and resulted in IgA dysfunction, as evidenced by decreased production and bacteria-binding capacity of IgA. Meanwhile, the disruptions of intestinal microflora and mucosal structure were exhibited. Transforming growth factor-β1 activated IgA CSR as evidenced by the increased activation molecules and IgA precursors. Strikingly, TGF-β1 improved intestinal mucosal IgA dysfunction, dysbiosis and epithelial damage at the early stage after reperfusion. In addition, SB-431542, a specific inhibitor of activating mothers against decapentaplegic homologue ( SMAD) 2/3, totally blocked the inductive effect of TGF-β1 on IgA CSR and almost abrogated the above protective effects on intestinal barriers. Taken together, our study demonstrates that TGF-β1 protects intestinal mucosal IgA immunity, microbiota and epithelial integrity against I/R injury mainly through TGF-β receptor 1/ SMAD 2/3 pathway. Induction of IgA CSR may be involved in the protection conferred by TGF-β1. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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