Activation of IGF-1/IGFBP-3 signaling by berberine improves intestinal mucosal barrier of rats with acute endotoxemia
Activation of IGF-1/IGFBP-3 signaling by berberine improves intestinal mucosal barrier of rats with acute endotoxemia
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DOI：
10.1016/j.fitote.2017.11.012
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发表时间：
2018-01-01
期刊：
影响因子：
3.4
通讯作者：
Feng, Aiwen
中科院分区：
文献类型：
--
作者：
He, Yan;Yuan, Xiaoming;Feng, Aiwen
胰岛素样生长因子 I (IGF-I) 和结合蛋白 3 (IGFBP-3) 在维持肠粘膜屏障功能中发挥作用。然而，在内毒素血症期间，小肠粘膜中的 IGF-I/IGFBP-3 和紧密连接蛋白 (TJP) 表达常常受损。在该急性内毒素血症模型中，评估了小檗碱对回肠粘膜中 IGF-I/IGFBP-3 和 TJP 表达的调节作用。研究结果表明，全身注射脂多糖（LPS）可抑制 IGF-I 和 IGFBP-3 的 mRNA 和蛋白质表达，但小檗碱可改善其产生。 LPS注射抑制occludin和claudin-1蛋白的生成，而LPS的这种抑制作用被小檗碱消除。 AG1024 或 siRNA 对 IGF-I/IGFBP-3 信号传导的抑制减少了小檗碱诱导的 occludin 和 claudin-1 的产生。此外，发现 GW9662 可以抑制小檗碱诱导的 IGF-I/IGFBP-3 表达，表明 PPAR γ 和 IGF-I/IGFBP-3 轴之间存在交联。
Insulin-like growth factor I (IGF-I) and binding protein 3 (IGFBP-3) play a role in the maintenance of gut mucosal barrier function. Nevertheless, IGF-I/IGFBP-3 and tight junction protein (TJP) expression in small intestinal mucosa are often impaired during endotoxemia. In this model of acute endotoxemia, the regulatory effect of berberine on IGF-I/IGFBP-3 and TJP expression in ileal mucosa was evaluated. The findings revealed systemic injection of lipopolysaccharide (LPS) suppressed mRNA and protein expression of IGF-I and IGFBP-3, but berberine ameliorated their production. LPS injection inhibited occludin and claudin-1 protein generation, and this inhibitory effect of LPS was abolished by berberine. Inhibition of IGF-I/IGFBP-3 signaling by AG1024 or siRNAs reduced berberine-induced occludin and claudin-1 production. Additionally, GW9662 was found to repress berberine-induced IGF-I/IGFBP-3 expression, indicating of a cross-link between PPAR gamma and IGF-I/IGFBP-3 axis.