Oue T, Puri P
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
J Pediatr Surg. 1999 Aug;34(8):1257-60. doi: 10.1016/s0022-3468(99)90163-x.
Recently, the endothelin-3 (EDN3) and endothelin-B receptor (EDNRB) gene have been recognized as susceptibility genes for Hirschsprung's disease (HD). However, gene mutations have been observed only in limited cases, and the role of EDN3 in the pathogenesis and motility dysfunction in HD is not understood fully. To evaluate the possible implication of EDN3 and EDNRB for the development of HD, we examined the EDN3 and EDNRB mRNA level in bowel specimens of HD patients.
Entire resected specimens of colon were obtained from 14 patients with HD. Eight age-matched control patients without gastroenteric disorders also were examined. mRNA was extracted from ganglionic and aganglionic segments of the HD specimens and normal colons. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the relative amount of EDN3 and EDNRB mRNA.
In normal colon, constant EDN3 and EDNRB mRNA expression was observed. In HD, EDN3 and EDNRB mRNA expression was observed. In HD, EDN3 and EDNRB mRNA levels were decreased both in ganglionic and aganglionic segment in 2 cases. In 6 cases, EDN3 mRNA expression was decreased in aganglionic segment and in another 2 cases, EDNRB mRNA expression was decreased in aganglionic segment. In the remaining 4 cases, EDN3 and EDNRB mRNA levels were similar to controls.
The authors' findings indicate that loss of EDN3 and EDNRB function may be involved in the maldevelopment of neural crest-derived cells causing HD in many patients.
最近，内皮素-3（EDN3）和内皮素B受体（EDNRB）基因已被确认为先天性巨结肠症（HD）的易感基因。然而，仅在有限的病例中观察到基因突变，并且EDN3在HD发病机制和运动功能障碍中的作用尚未完全明确。为了评估EDN3和EDNRB在HD发生发展中的可能影响，我们检测了HD患者肠标本中EDN3和EDNRB的mRNA水平。
从14例HD患者中获取整个切除的结肠标本。还检查了8例年龄匹配、无胃肠疾病的对照患者。从HD标本的神经节段和无神经节段以及正常结肠中提取mRNA。进行逆转录聚合酶链反应（RT-PCR）以评估EDN3和EDNRB mRNA的相对量。
在正常结肠中，观察到EDN3和EDNRB mRNA持续表达。在HD中，也观察到EDN3和EDNRB mRNA表达。在HD中，2例患者的神经节段和无神经节段中EDN3和EDNRB mRNA水平均降低。6例患者的无神经节段中EDN3 mRNA表达降低，另外2例患者的无神经节段中EDNRB mRNA表达降低。其余4例患者中，EDN3和EDNRB mRNA水平与对照组相似。
作者的研究结果表明，EDN3和EDNRB功能丧失可能与许多患者中导致HD的神经嵴衍生细胞发育异常有关。
