Greig Chasen J, Cowles Robert A
Section of Pediatric Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT.
Section of Pediatric Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT.
J Pediatr Surg. 2017 Jun;52(6):1031-1034. doi: 10.1016/j.jpedsurg.2017.03.037. Epub 2017 Mar 18.
Intestinal mucosal homeostasis is controlled by multiple factors and an intact, functional mucosa is essential for survival. Maintenance of the epithelium begins with crypt base stem cells which eventually give rise to all epithelial cell types. Evidence suggests an important role of the enteric cholinergic nervous system in these processes. We hypothesized that mice with altered muscarinic signaling would exhibit differences in mucosal morphometric and proliferative parameters compared to wild-type mice.
Mouse lines specifically deficient in one of the five muscarinic acetylcholine receptors (M1KO-M5KO) were used for experiments. Distal ileal segments were obtained and histologic sections created. Villus height and crypt depth were measured using H&E-stained sections, while crypt proliferation index (CPI) was calculated using Ki67-stained sections.
The ileal mucosa from mice deficient in mAChRs exhibited differences from wild-type ileal mucosa in nearly all measured parameters. Knockout of mAChR2, mAChR3 and mAChR5 resulted in changes in all measured parameters. Ileal mucosa from M2KO mice showed an unexpected combination decreased VH but paradoxically increased CD and CPI.
Alterations in mAChR signaling causes change in ileal mucosal morphometry and crypt cell proliferation. While all mAChR subtypes may be involved, mAChR2, mAChR3, and mAChR5 appear to be critical for mucosal homeostasis. Further characterization of these pathways is warranted.
肠道黏膜稳态受多种因素控制，完整且功能正常的黏膜对生存至关重要。上皮细胞的维持始于隐窝底部干细胞，这些干细胞最终可分化为所有上皮细胞类型。有证据表明，肠道胆碱能神经系统在这些过程中发挥重要作用。我们推测，与野生型小鼠相比，毒蕈碱信号改变的小鼠在黏膜形态计量学和增殖参数方面会表现出差异。
使用特异性缺乏五种毒蕈碱型乙酰胆碱受体之一（M1KO - M5KO）的小鼠品系进行实验。获取回肠远端节段并制作组织学切片。使用苏木精和伊红（H&E）染色切片测量绒毛高度和隐窝深度，同时使用Ki67染色切片计算隐窝增殖指数（CPI）。
缺乏毒蕈碱型乙酰胆碱受体（mAChRs）的小鼠回肠黏膜在几乎所有测量参数上均与野生型回肠黏膜存在差异。敲除mAChR2、mAChR3和mAChR5导致所有测量参数发生变化。M2KO小鼠的回肠黏膜出现了意想不到的组合变化，即绒毛高度降低，但隐窝深度和增殖指数却反常增加。
mAChR信号的改变会导致回肠黏膜形态计量学和隐窝细胞增殖发生变化。虽然所有mAChR亚型可能都参与其中，但mAChR2、mAChR3和mAChR5似乎对黏膜稳态至关重要。有必要对这些途径进行进一步的表征。
