Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
GI Care for Kids, LLC, Children's Center for Digestive Healthcare, LLC, Atlanta, GA.
J Pediatr Gastroenterol Nutr. 2021 Dec 1;73(6):703-709. doi: 10.1097/MPG.0000000000003296.
Guanylate cyclase-C (GC-C) agonists, which increase intestinal secretion and accelerate transit, are used to treat chronic constipation and constipation-predominant irritable bowel syndrome and are being evaluated for pediatric use. Prior studies suggest GC-C receptor density may be higher in young children, potentially amplifying GC-C agonism with treatment implications. We aimed to quantitate duodenal and colonic GC-C mRNA expression in children.
Mucosal biopsies were obtained from subjects aged 6 months to 18 years during clinically indicated upper, that is, esophago-gastro-duodenal, and/or colonic endoscopy. Tissue samples without histologic abnormalities were grouped by subject age (<24 months, 24 months to <6 years, 6 to <12 years, and 12 to <18 years) and analyzed for GC-C mRNA expression by qPCR. The relationship between GC-C mRNA levels and age was modeled using regression analyses.
Ninety-nine subjects underwent upper endoscopy/colonoscopy; 93 had evaluable samples. Mean relative GC-C mRNA expression was 2.36 (range 2.21-2.46) for duodenal samples and 1.56 (range 1.22-1.91) for colonic samples. Predicted and observed normalized GC-C mRNA expression in each region were comparable among age groups. Pooled expression by region demonstrated lower expression in colonic versus duodenal samples.
Uniform levels of GC-C mRNA expression were detected in children aged >6 months in the duodenum and >12 months in the colon. Higher expression was observed in all age groups in duodenal versus colonic samples, indicating regional variability in GC-C receptor density. These data are reassuring for further studies of GC-C agonists in children.
鸟苷酸环化酶-C（GC-C）激动剂可增加肠道分泌并加速转运，用于治疗慢性便秘和以便秘为主的肠易激综合征，目前正在评估其在儿科的应用。先前的研究表明，GC-C 受体密度在幼儿中可能更高，这可能会放大 GC-C 激动剂的作用，具有治疗意义。我们旨在定量测定儿童十二指肠和结肠 GC-C mRNA 的表达。
在临床指征性上消化道（即食管-胃-十二指肠）和/或结肠镜检查期间，从 6 个月至 18 岁的受试者中获取黏膜活检样本。将无组织学异常的组织样本按受试者年龄（<24 个月、24 个月至<6 岁、6 至<12 岁和 12 至<18 岁）分组，并通过 qPCR 分析 GC-C mRNA 的表达。使用回归分析对 GC-C mRNA 水平与年龄的关系进行建模。
99 例受试者行上消化道/结肠镜检查，93 例有可评估的样本。十二指肠样本的平均相对 GC-C mRNA 表达为 2.36（范围 2.21-2.46），结肠样本为 1.56（范围 1.22-1.91）。各年龄组的预测和观察到的标准化 GC-C mRNA 表达在区域内具有可比性。按区域汇总的表达显示，结肠样本的表达低于十二指肠样本。
6 个月大的儿童在十二指肠和>12 个月大的儿童在结肠中均检测到 GC-C mRNA 表达水平一致。在所有年龄组中，十二指肠样本的表达均高于结肠样本，表明 GC-C 受体密度存在区域性差异。这些数据为进一步研究 GC-C 激动剂在儿童中的应用提供了保证。
