title: BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit.
abstract: The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF(+/-) mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently, and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity, and this process is likely initiated by BDNF-TrkB pathway activation.
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.|Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.|Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.|Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.
authors.forename: Fei-Xue
authors.initials: FX
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.|Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.|Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Yu
authors.affiliation: Department of Physiology, Shandong University School of Medicine, Jinan 250012, P. R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Han
authors.affiliation: Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Suhail
authors.initials: S
authors.lastname: Akhtar
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.|Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Zuo
authors.affiliation: Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Xiao-Di
authors.initials: XD
authors.lastname: Tan
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.|Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, P. R. China.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D020813:Receptor, trkB; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; C579455:BDNF protein, human; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human
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