Loss of sensory and noradrenergic innervation in benign colorectal adenomatous polyps-a putative role of semaphorins 3F and 3A

N Graf, Mairi Hall McLean, S Capellino, J Scholmerich, Graeme Ian Murray, Emad Munir El-Omar, R.H. Straub

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Background Nerve fibers can exert trophic/anti-trophic effects on epithelial cells. Substance P (SP) is a pro-proliferative neuropeptide, whereas sympathetic noradrenaline is anti-proliferative at high concentrations. Methods Density of noradrenergic and sensory nerve fibers and presence of nerve repellent factors specific for noradrenergic (semaphorin 3F) and sensory nerve fibers (semaphorin 3A) were investigated in colorectal adenomas. Key Results The pedunculus was innervated by noradrenergic fibers, whereas the mucosa was sparsely innervated. The control submucosa compared with control mucosa demonstrated increased density of noradrenergic fibers. Control tissue was much better innervated than the polyp. This was accompanied by strong expression of semaphorin 3F in epithelial cells. Density of sensory SP+ nerve fibers was higher in control colon mucosa compared with polyp mucosa, and SP+ cell clusters and semaphorin 3A-positive cells appeared in the intercrypt space in polyps, but not in control tissue. Conclusions & Inferences This study demonstrated a marked loss of noradrenergic and sensory nerve fibers in polyp mucosa, which was associated with a strong increase of semaphorin 3F and 3A. Up-regulation of the sympathetic repellent semaphorin 3F in the polyps possibly triggers sympathetic repulsion and polyp growth due to the loss of anti-proliferative noradrenaline and presence of SP from local SP+ cells.

Original languageEnglish
Pages (from-to)120-e83
Number of pages10
JournalNeurogastroenterology and Motility
Issue number2
Early online date16 Nov 2011
Publication statusPublished - Feb 2012



  • adenomatous colon polyp
  • noradrenaline
  • semaphorins
  • sensory nervous system
  • substance P
  • sympathetic nervous system

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