N-butyrate increases heat shock protein 70 through heat shock factor 1 and AMP-activated protein kinase pathways in human intestinal Caco-2 cells
N-butyrate increases heat shock protein 70 through heat shock factor 1 and AMP-activated protein kinase pathways in human intestinal Caco-2 cells
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DOI：
10.1016/j.abb.2023.109525
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发表时间：
2023-02-07
影响因子：
3.9
通讯作者：
Suzuki, Takuya
中科院分区：
文献类型：
--
作者：
Adesina, Precious Adedayo;Saeki, Itsuki;Suzuki, Takuya
肠道上皮完整性受损是引起肠道和肠外疾病的原因之一。热休克蛋白70(HSP70)是一种细胞保护蛋白，在维持肠道内环境稳定方面发挥着重要作用。HSP70在肠道中的表达与局部微生物区系有关。本研究探讨了人肠道Caco-2细胞中肠道微生物区系的主要代谢物正丁酸上调HSP70的分子机制。正丁酸处理Caco-2细胞后，HSP70蛋白和信使核糖核酸水平呈剂量依赖性上调。利用荧光素酶报告实验发现，正丁酸增强了HSP70的转录活性。这些效应对转录因子热休克因子1(HSF1)和AMP激活的蛋白激酶(AMPK)的抑制很敏感。正丁酸可增加HSF1和AMPK的磷酸化活性。综上所述，本研究表明正丁酸部分参与了依赖微生物区系的HSP70的肠道表达，并且这种影响是通过HSF1和AMPK途径发挥的。
Impaired integrity of the intestinal epithelium is a cause of intestinal and extraintestinal diseases. Heat shock protein 70 (HSP70), a cytoprotective protein, plays an important role in maintaining intestinal homeostasis. The intestinal expression of HSP70 is linked with the local microbiota. The present study investigated the molecular mechanisms underlying the upregulation of HSP70 by n-butyrate, a major metabolite of the intestinal microbiota in human intestinal Caco-2 cells. Treatment of Caco-2 cells with n-butyrate upregulated HSP70 protein and mRNA levels in a dose-dependent manner. Using luciferase reporter assay, it was found that n-butyrate enhanced the transcriptional activity of HSP70. These effects were sensitive to the inhibition of heat shock factor 1 (HSF1), a transcription factor, and AMP-activated protein kinase (AMPK). N-butyrate increased the phosphorylation (activity) of HSF1 and AMPK. Taken together, this study shows that n-butyrate is partly involved in the microbiota-dependent intestinal expression of HSP70, and the effect is exerted through the HSF1 and AMPK pathways.