title: Elevated expression of c-fos in central nervous system correlates with visceral hypersensitivity in irritable bowel syndrome (IBS): a new target for IBS treatment.
abstract: OBJECTIVE
  Although visceral hypersensitivity is a major pathophysiological feature of irritable bowel syndrome (IBS), its molecular mechanisms are still poorly understood. c-fos is a well-established marker of cell activation. Accumulating evidence demonstrates that norepinephrine (NE) system is dysregulated in IBS; however, very little is known on its mechanism. It is our hypothesis that elevated expression of c-fos in central nervous system (CNS) correlates with visceral hypersensitivity in rat model of IBS. Furthermore, we explored the changes of NE system in IBS patients.
  
  
  METHODS
  The rat model of IBS was induced by heterotypic chronic and acute stress. Tissues obtained from rat model were analyzed for c-fos levels in CNS (frontal lobe, hippocampus, cornu dorsale) and colon by immunohistochemistry. Real-time reverse transcription polymerase chain reaction was used to detect tyrosine hydroxylase (TH) in the colonic tissues obtained from IBS patients.
  
  
  RESULTS
  The rat model of IBS was associated with increased expression of c-fos in different parts of CNS (P = 0.001, P = 0.002, and P = 0.002, respectively), but normal in colon (P = 0.207). The clinical parameters (colonic motility and sensation) of rat model were significantly correlated with elevated c-fos in CNS (P < 0.05). Enterochromaffin cells and serotonin in colon were related to the elevated c-fos in CNS (P < 0.05). The TH messenger ribonucleic acid (mRNA level of IBS-D patients was almost four times as much as that of controls.
  
  
  CONCLUSIONS
  Elevated expression of c-fos in CNS might be one of key mechanisms in etiology of IBS. Therefore, regulation of CNS activation could be a major targeting effect when treating IBS patients.
authors.affiliation: Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1 Shuaifuyuan Wangfujing Street, Beijing, 100730, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Zou
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Lv
authors.forename: Jing
authors.initials: J
authors.lastname: Wei
authors.forename: Xiu-Cai
authors.initials: XC
authors.lastname: Fang
authors.forename: Jia-Ming
authors.initials: JM
authors.lastname: Qian
mesh_terms: D000328:Adult; D000818:Animals; D001007:Anxiety / Q000150:complications; D016022:Case-Control Studies; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003863:Depression / Q000150:complications; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000150:complications*; D043183:Irritable Bowel Syndrome / Q000150:complications* / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D014781:Viscera / Q000473:pathology*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase