Enhanced serotonin signaling stimulates ordered intestinal mucosal growth

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• 作者：John J. Tackett ; MD ; MHS ; Neeru Gandotra ; PhD ; Michaela C. Bamdad ; MD ; MHS ; Eleanor D. Muise ; MD ; Robert A. Cowles ; MD ; ^{robert.cowles@yale.edu}
• 关键词：Serotonin ; Intestine ; Mucosa ; Short bowel syndrome ; Enteric nervous system
• 刊名：Journal of Surgical Research
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：208
• 期：Complete
• 页码：198-203
• 全文大小：1265 K
• 卷排序：208

文摘

Significant quantities of serotonin (5-hydroxytryptamine; 5-HT) are found in the intestine, and studies have demonstrated that 5-HT can stimulate enterocyte cell division, suggesting regulatory roles in mucosal homeostasis and intestinal adaptation. We hypothesized that excess enteric 5-HT signaling enhances mucosal growth without changing intestinal villous cellular makeup.MethodsMice lacking the serotonin reuptake transporter (SERT) and wild-type littermates (WTLM) were euthanized and their ileum analyzed. Villus height (VH), crypt depth (CD), and enterocyte height (EH) were measured. Enterocyte cell division was measured using Ki-67 immunofluorescence to calculate crypt proliferation index (CPI). Cellular distribution along villi was investigated by immunofluorescent staining for enterocytes, enteroendocrine cells, and goblet cells. Group measurements were compared using t-test and chi-squared test.ResultsSERT knock-out (SERTKO) mice had significantly taller villi, deeper crypts, and taller enterocytes compared with WTLM (P < 0.0001). Similarly, enterocyte proliferation was greater in SERTKO compared with WTLM (P < 0.01). For SERTKO, mean values were: VH, 255.6 μm; CD, 66.7 μm; EH, 21.2 μm; and CPI, 52.8%. For WTLM, corresponding values were: VH, 207.8 μm; CD, 56.1 μm; EH, 19.5 μm; and CPI, 31.9%. The cellular composition along villi was not significantly different between genotypes (P > 0.05).ConclusionsEnhancing 5-HT signaling in mice increases VH, CD, EH, and crypt cell proliferation in the intestinal mucosa. 5-HT-associated growth did not alter the cellular composition of the villi. Serotonin may represent an important physiologic regulator of intestinal growth and adaptation and holds promise as a target for therapies aimed at enhancing intestinal recovery after injury or mucosal surface area loss.