Artikel
Outlet obstruction – a disease of the enteric nervous system?
Suche in Medline nach
Autoren
Veröffentlicht: | 21. April 2016 |
---|
Gliederung
Text
Background: Chronic constipation is a common disease with a prevalence of up to 18% and associated with a high socioeconomic burden. In these patients a rectal prolapse is often present. The underlying pathophysiology of its development is still unknown. Purpose of this study is to analyse human rectal prolapse and its association with changes of the enteric nervous system.
Materials and methods: Human full thickness rectal wall samples of three patients with internal rectal prolapse were analyzed by RT-qPCR and by differentiated transcriptome sequencing (Next Generation Sequencing) and compared to non constipated controls. Therefore first quality controls of RNA was performed by Agilent Bioanalyzer, then cDNA library for sequencing of the transcriptome were established (TruSeq RNA Sample), before single-end sequencing by Illumina HiSeq 2500 was performed.
Results: 820 Mio high quality reads were performed. Principal component analysis confirmed the homogeneity of the samples. Differential gene expression profiling showed that 1699 genes were significantly down regulated in prolapse samples (p<0.05). Considering only these genes that were highly significantly down regulated (p<0.001) in the gene ontology analysis, especially neuronal associated genes were affected regarding biological pathways, cellular components, and ligan-receptor interaction. These genes were associated with the aganglionosis M. Hirschsprung, and with the enteric nervous system as NOS1, CHAT, GDNF, and RET. These result were confirmed in the RT-qPCR analysis.
Conclusion: Next generation sequencing showed that in patients with chronic constipation on the basis of an internal rectal prolapse, neuronal associated genes were highly disregulated. This might indicate that outlet obstruction is a disease of the enteric nervous system.