Tackett John J, Gandotra Neeru, Bamdad Michaela C, Muise Eleanor D, Cowles Robert A
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut.
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut.
J Surg Res. 2017 Feb;208:198-203. doi: 10.1016/j.jss.2016.09.036. Epub 2016 Sep 28.
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.
Mice 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.
SERT 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).
Enhancing 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.
在肠道中发现了大量的血清素（5-羟色胺；5-HT），并且研究表明5-HT可以刺激肠上皮细胞分裂，提示其在黏膜稳态和肠道适应性方面具有调节作用。我们推测，过量的肠道5-HT信号传导可增强黏膜生长，而不改变肠绒毛细胞组成。
对缺乏血清素再摄取转运体（SERT）的小鼠和野生型同窝小鼠（WTLM）实施安乐死，并对其回肠进行分析。测量绒毛高度（VH）、隐窝深度（CD）和肠上皮细胞高度（EH）。使用Ki-67免疫荧光法测量肠上皮细胞分裂，以计算隐窝增殖指数（CPI）。通过对肠上皮细胞、肠内分泌细胞和杯状细胞进行免疫荧光染色，研究沿绒毛的细胞分布。使用t检验和卡方检验比较组间测量值。
与WTLM相比，SERT基因敲除（SERTKO）小鼠的绒毛显著更高、隐窝更深、肠上皮细胞更高（P < 0.0001）。同样，与WTLM相比，SERTKO小鼠的肠上皮细胞增殖也更明显（P < 0.01）。SERTKO小鼠的平均值为：VH，255.6μm；CD，66.7μm；EH，21.2μm；CPI，52.8%。WTLM小鼠的相应值为：VH，207.8μm；CD，56.1μm；EH，19.5μm；CPI，31.9%。不同基因型之间沿绒毛的细胞组成无显著差异（P > 0.05）。
增强小鼠体内的5-HT信号传导可增加肠道黏膜的VH、CD、EH和隐窝细胞增殖。5-HT相关的生长并未改变绒毛的细胞组成。血清素可能是肠道生长和适应性的重要生理调节因子，有望成为旨在促进损伤后肠道恢复或黏膜表面积损失后肠道恢复的治疗靶点。
