neuropeptide-y and Crohn-Disease

Crohn's disease (CD) is a type of inflammatory bowel disease that cannot be fully cured by medication or surgery. In the present study, the aim was to understand the underlying mechanisms of CD. Two CD microarray datasets were downloaded from The Gene Expression Omnibus database: GSE36807 (13 CD and 7 normal samples) and GSE59071 (8 CD and 11 normal samples). A series of bioinformatics analyses were conducted, including weighted gene co‑expression network analysis to identify stable modules, and analysis of differentially expressed genes (DEGs) between CD and normal samples. The common DEGs in the GSE36807 and GSE59071 datasets were screened. Subsequently, overlapping genes in the stable modules and the DEGs were selected to construct a protein‑protein interaction (PPI) network using Cytoscape software. Enrichment analysis of genes in the network was performed to explore their biological functions. A total of 10 stable modules and 927 DEGs were identified, of which 234 genes were shared in the stable modules and the DEGs. After removal of 32 uncharacterized genes, 202 genes were selected to build the PPI network. Low density lipoprotein receptor (LDLR), toll‑like receptor 2 (TLR2), lipoprotein lipase (LPL), forkhead box protein M1 (FOXM1) and neuropeptide Y (NPY) were revealed as key nodes with high degree. Pathway enrichment analysis demonstrated that LPL was enriched in the peroxisome proliferator‑activated receptor (PPAR) signaling pathway. In conclusion, LDLR, TLR2, FOXM1 and NPY, as well as LPL in the PPAR signaling pathway may serve critical roles in the pathogenesis of CD.

Topics: Computational Biology; Crohn Disease; Databases, Genetic; Forkhead Box Protein M1; Gene Regulatory Networks; Humans; Lipoprotein Lipase; Neuropeptide Y; Peroxisome Proliferator-Activated Receptors; Protein Interaction Maps; Receptors, LDL; Signal Transduction; Toll-Like Receptor 2; Transcriptome

There have been conflicting results regarding the effect of Crohn's disease on the neurochemical composition of the enteric nervous system.. To examine the effect of Crohn's disease on the neurochemical composition of enteric nerve fibres and cell bodies using whole mount preparations of human ileum.. Whole wall ileum from seven normal subjects and nine patients with Crohn's disease was used to investigate the neurochemical composition of neurones and nerve fibres in the myenteric plexus, circular muscle, and serosa layer of ileum using immunohistochemical techniques.. Increased tyrosine hydroxylase, 5-hydroxytryptamine, and neuropeptide Y immunoreactivity was exclusively seen in the myenteric plexus. There was increased neurofilament immunoreactivity in the myenteric plexus and nerve fibres of the circular muscle layer, and thick bundles of immunoreactive nerve fibres in the serosa layer. Increased vasoactive intestinal polypeptide, nitric oxide synthase, and pituitary adenylate cyclase activating peptide immunoreactivity was seen in the myenteric plexus and nerve fibres of the circular muscle layer, and aggregates of inflammatory cells in the serosa layer of the afflicted segment of Crohn's ileum. In addition, there was a chaotic display of nerve fibres containing some of the neuroactive substances with a high frequency of enlarged varicosities in the myenteric ganglia and/or nerve fibres of the circular muscle layer of Crohn's ileum.. Results show quantitative as well as qualitative changes in the neurochemical composition of enteric nerve fibres and nerve cell bodies of Crohn's ileum. These changes and the presence of nitric oxide synthase and peptides immunoreactive inflammatory cells in the serosa layer suggest that nerve-immune interactions may have a significant role in the process of the inflammatory changes seen in Crohn's ileitis.

Topics: Adult; Aged; Crohn Disease; Enteric Nervous System; Fluorescent Antibody Technique, Indirect; Humans; Ileitis; Ileum; Image Processing, Computer-Assisted; Middle Aged; Neuropeptide Y; Neuropeptides; Neurotransmitter Agents; Nitric Oxide Synthase; Pituitary Adenylate Cyclase-Activating Polypeptide; Serotonin; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide