目的: 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.

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