在线客服: 点击这里给我发消息  新用户使用步骤:会员注册→充值→重新登入→进入资源
标题:LKB1-AMPK modulates nutrient-induced changes in the mode of division of intestinal epithelial crypt cells in mice.
时间:2019-11-19 21:31:15
DOI:10.1177/1535370217724427
PMID:28766983
作者:Blackmore K;Zhou W;Dailey MJ
摘要:Abstract Nutrient availability influences intestinal epithelial stem cell proliferation and tissue growth. Increases in food result in a greater number of epithelial cells, villi height and crypt depth. We investigated whether this nutrient-driven expansion of the tissue is the result of a change in the mode of intestinal epithelial stem cell division and if LKB1-AMPK signaling plays a role. We utilized in vivo and in vitro experiments to test this hypothesis. C57BL/6J mice were separated into four groups and fed varying amounts of chow for 18 h: (1) ad libitum, (2) 50% of their average daily intake (3) fasted or (4) fasted for 12 h and refed. Mice were sacrificed, intestinal sections excised and immunohistochemically processed to determine the mitotic spindle orientation. Epithelial organoids in vitro were treated with no (0 mM), low (5 mM) or high (20 mM) amounts of glucose with or without an activator (Metformin) or inhibitor (Compound C) of LKB1-AMPK signaling. Cells were then processed to determine the mode of stem cell division. Fasted mice show a greater % of asymmetrically dividing cells compared with the other feeding groups. Organoids incubated with 0 mM glucose resulted in a greater % of asymmetrically dividing cells compared with the low or high-glucose conditions. In addition, LKB1-AMPK activation attenuated the % of symmetric division normally seen in high-glucose conditions. In contrast, LKB1-AMPK inhibition attenuated the % of asymmetric division normally seen in no glucose conditions. These data suggest that nutrient availability dictates the mode of division and that LKB1-AMPK mediates this nutrient-driven effect on intestinal epithelial stem cell proliferation. Impact statement The underlying cell biology of changes in the polarity of mitotic spindles and its relevance to tissue growth is a new concept and, thus, these data provide novel findings to begin to explain how this process contributes to the regeneration and growth of tissues. We find that short-term changes in food intake in vivo or glucose availability in vitro dictate the mode of division of crypt cells. In addition, we find that LKB1-AMPK signaling modulates the glucose-induced changes in the mode of division in vitro. Identifying mechanisms involved in the mode of division may provide new targets to control tissue growth.
大小:496 kb
页数:10 PAGES
下载: 点击下载
预览:

浏览器不支持嵌入PDF阅读,打开新页面在线阅读

本页内容由网络收集而来,版权归原创者所有,如有侵权请及时联系