Riboflavin Depletion Impairs Cell Proliferation in Adult Human Duodenum: Identification of Potential Effectors
Riboflavin Depletion Impairs Cell Proliferation in Adult Human Duodenum: Identification of Potential Effectors
复制标题
DOI：
10.1007/s10620-010-1374-3
复制
发表时间：
2011-04-01
影响因子：
3.1
通讯作者：
Corfe, Bernard M.
中科院分区：
文献类型：
--
作者：
Nakano, Emi;Mushtaq, Sohail;Corfe, Bernard M.
核黄素（维生素B-2）是一种重要的膳食成分，在氧化代谢中具有已知的功能。我们先前使用核黄素缺乏的大鼠模型的数据表明，核黄素也作为一种管腔信号分子调节隐窝发育和细胞周转。核黄素缺乏症在地球仪的高收入和低收入国家都很普遍。本研究旨在确定核黄素缺乏是否对成人胃肠道（GI）形态产生影响，以及任何此类改变的影响和效应可能是什么。十二指肠活检和血液样本收集自胃镜检查患者的横截面。通过免疫组织化学研究隐窝形态和细胞分裂，并测定生化核黄素状态。此外，我们还建立了一个核黄素缺乏的细胞培养模型，并结合流式细胞术、微阵列和克隆形成试验进行了分析。（P = 0.023），细胞较少（P = 0.007），细胞分裂较少（P = 0.034）。培养的结肠细胞在核黄素耗尽后，细胞周期减慢。显微镜检查显示有丝分裂受损和非整倍体细胞的积累。基因表达谱的改变反映了这种改变，几个有丝分裂相关基因改变，包括AspM，细胞周期蛋白B1，Birc 5下调和Kif 23上调。体外核黄素缺乏导致细胞增殖能力的不可逆丧失。成年人核黄素缺乏会损害肠细胞的增殖和增殖能力，这可能对胃肠道功能有影响。
Riboflavin (vitamin B-2) is an essential dietary component with a known function in oxidative metabolism. Our previous data using a rat model of riboflavin deficiency suggested that riboflavin also functions as a luminal signaling molecule regulating crypt development and cell turnover. Riboflavin deficiency is prevalent in both high- and low-income countries across the globe. This study aims to establish whether riboflavin deficiency has consequences for gastrointestinal (GI) morphology in adults and what the effects and effectors of any such alteration may be.Duodenal biopsies and blood samples were collected from a cross-section of gastroscopy patients. Crypt morphology and cell division were studied by immunohistochemistry, and biochemical riboflavin status was determined. Additionally a cell culture model of riboflavin deficiency was developed and analyzed using a combination of flow cytometry, and microarray and clonogenic assays.Duodenal crypts from subjects in the lowest quartile of riboflavin status were significantly shorter (P = 0.023), less cellular (P = 0.007), and had fewer cell divisions (P = 0.034) than the crypts of subjects in the top quartile of riboflavin status. Following riboflavin depletion of colon cells in culture, cell cycle slowed. Microscopy revealed impaired mitosis and accumulation of aneuploid cells. Alterations in gene expression profiles reflected this alteration, with several mitosis-related genes altered, including AspM, cyclin B1, and Birc5 downregulated and Kif23 upregulated. Riboflavin depletion in vitro caused irreversible loss of proliferative potential of cells.Riboflavin depletion in adult humans impairs proliferation and proliferative potential of intestinal cells, which may have implications for gastrointestinal function.