生长激素和谷氨酰胺对肠干细胞激活的不同影响。

Distinct Effects of Growth Hormone and Glutamine on Activation of Intestinal Stem Cells.

机构信息

Department of Surgery, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei, Taiwan.

Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li, Taoyuan, Taiwan.

出版信息

JPEN J Parenter Enteral Nutr. 2018 Mar;42(3):642-651. doi: 10.1177/0148607117709435. Epub 2017 Dec 19.

DOI:10.1177/0148607117709435

PMID:28510488

Abstract

BACKGROUND

For patients with short bowel syndrome under parenteral nutrition support, growth hormone (GH) and glutamine (GLN) have been found to help the growth of intestinal mucosa. In this research, we studied the effects of GH and GLN on intestinal stem cells (ISCs).

METHODS

The in vitro and in vivo effects of GH and/or GLN on ISCs were evaluated by observing the ability of ISCs to form organoids in a Matrigel culture system. The expression levels of stemness and differentiation markers in ISCs and organoids were assessed using quantitative real-time polymerase chain reaction, immunofluorescence assay, and immunohistochemistry staining.

RESULTS

In vitro administration of GH activated the stemness of ISCs, whereas GLN enhanced the expression of chromogranin A and Muc2, which are differentiation markers in enteroendocrine and goblet cells, respectively. Administration of GH or GLN in mice showed that GH, but not GLN, upregulated the proliferative activity of ISCs with increased formation of crypt organoids. In addition, GH increased the expression of Lgr5 and GLN enhanced expression of Muc2 in the crypt fractions of the intestines in mice.

CONCLUSION

These results suggest that GH mainly enhances proliferative activities, whereas GLN promotes the differentiation potential of ISCs.

摘要

背景

对于接受肠外营养支持的短肠综合征患者，生长激素（GH）和谷氨酰胺（GLN）已被发现有助于肠黏膜生长。在这项研究中，我们研究了 GH 和 GLN 对肠干细胞（ISCs）的影响。

方法

通过观察 ISCs 在 Matrigel 培养系统中形成类器官的能力，评估 GH 和/或 GLN 对 ISCs 的体外和体内作用。使用实时定量聚合酶链反应、免疫荧光分析和免疫组织化学染色评估 ISCs 和类器官中干性和分化标志物的表达水平。

结果

体外给予 GH 激活了 ISCs 的干性，而 GLN 增强了分别代表肠内分泌细胞和杯状细胞分化标志物的嗜铬粒蛋白 A 和 Muc2 的表达。在小鼠中给予 GH 或 GLN 后，结果表明 GH 而非 GLN 增加了 ISCs 的增殖活性，导致隐窝类器官形成增加。此外，GH 增加了 Lgr5 的表达，GLN 增强了 Muc2 在小鼠肠道隐窝部分的表达。