title: Loss of sensory and noradrenergic innervation in benign colorectal adenomatous polyps--a putative role of semaphorins 3F and 3A.
abstract: 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.
  
  
  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
  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.
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Graf
authors.forename: M
authors.initials: M
authors.lastname: McLean
authors.forename: S
authors.initials: S
authors.lastname: Capellino
authors.forename: J
authors.initials: J
authors.lastname: Schölmerich
authors.forename: G I
authors.initials: GI
authors.lastname: Murray
authors.forename: E M
authors.initials: EM
authors.lastname: El-Omar
authors.forename: R H
authors.initials: RH
authors.lastname: Straub
mesh_terms: D018256:Adenomatous Polyps / Q000235:genetics / Q000378:metabolism*; D000320:Adrenergic Fibers / Q000378:metabolism*; D003106:Colon / Q000294:innervation* / Q000378:metabolism; D003111:Colonic Polyps / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000294:innervation / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012007:Rectum / Q000294:innervation* / Q000378:metabolism; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C491230:SEMA3F protein, human; D040121:Semaphorin-3A