Mutual regulation between butyrate and hypoxia-inducible factor-1 alpha in epithelial cell promotes expression of tight junction proteins
Mutual regulation between butyrate and hypoxia-inducible factor-1 alpha in epithelial cell promotes expression of tight junction proteins
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上皮细胞中丁酸盐和缺氧诱导因子1α之间的相互调节促进紧密连接蛋白的表达
DOI：
10.1002/cbin.11336
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发表时间：
2020
影响因子：
3.9
通讯作者：
Yang Hua
中科院分区：
文献类型：
--
作者：
Yin Jiuheng;Zhou Chao;Yang Kunqiu;Ren Yanbei;Qiu Yuan;Xu Pengyuan;Xiao Weidong;Yang Hua
炎症性肠病是一种多病因的慢性疾病，由多方面因素驱动。缺氧诱导因子-1 α（HIF-1α）在缺氧的抗炎和细胞反应中起重要作用。先前的研究发现，B或T细胞特异性HIF-1α敲除小鼠表现出严重的结肠炎症。然而，我们对HIF-1α在肠上皮细胞（IEC）中的其他功能知之甚少。本研究以HIF-1αΔ IEC小鼠为研究对象，研究HIF-1α在IEC中的作用。通过用小干扰（si）RNA转染，在Caco-2细胞中敲低HIF-1α。采用免疫组化染色和蛋白质印迹法检测闭合小带-1（ZO-1）和Occludin的表达。收获结肠内容物进行高效液相色谱分析，以检查肠道中丁酸盐的水平。我们的研究发现，HIF-1α在葡聚糖硫酸钠诱导的结肠炎中发挥保护作用，这部分是由于其调节紧密连接（TJ）蛋白的表达。进一步的研究表明，HIF-1α通过调节丁酸含量来介导TJ蛋白水平。此外，我们发现丁酸盐调节TJ蛋白表达，这依赖于HIF-1α。这些结果表明丁酸盐与HIF-1α之间存在相互调节机制，在维持胃肠道屏障功能方面具有重要作用。
Inflammatory bowel disease is a kind of multi‐aetiological chronic disease that is driven by multidimensional factors. Hypoxia‐inducible factor‐1α (HIF‐1α) plays an important role in anti‐inflammatory and cellular responses to hypoxia. Previous studies have found that B or T‐cell‐specific HIF‐1α knock out mice exhibit severe colonic inflammation. However, we know very little about other functions of HIF‐1α in intestinal epithelial cells (IECs). In our study, HIF‐1αΔIECmice were used to study the function of HIF‐1α in IECs. HIF‐1α was knocked down in Caco‐2 cells by transfection with a small interfering (si) RNA. Immunohistochemical staining and western blotting were used to detect the expression of zonula occluden‐1 (ZO‐1) and Occludin. The content of colon was harvested for high‐performance liquid chromatography analysis to examine the levels of butyrate in the gut. Our research found that HIF‐1α played a protective role in dextran sulphate sodium‐induced colitis, which was partly due to its regulation of tight junction (TJ) protein expression. Further study revealed that HIF‐1α mediated TJ proteins levels by moderating the content of butyrate. Moreover, we found that butyrate regulated TJ protein expression, which is dependent on HIF‐1α. These results indicated that there is a mutual regulatory mechanism between butyrate and HIF‐1α, which has an important role in the maintenance of barrier function of the gastrointestinal tract.