title: BDNF modulates intestinal barrier integrity through regulating the expression of tight junction proteins.
abstract: BACKGROUND
  Brain-derived neurotrophic factor (BDNF) may play a vital role in the homeostatic regulation of intestinal barrier integrity. We aimed to investigate the physiological role of BDNF in maintaining the intestinal epithelial barrier using postinflammatory irritable bowel syndrome (PI-IBS) mice and explore the underlying molecular mechanisms using intestinal epithelial cells in vitro.
  
  
  METHODS
  Postinflammatory-IBS mice were induced by intrarectal administration of trinitrobenzene sulfonic acid and allowed to recover for 28 days. Frequency of defecation, fecal water content, colonic epithelial integrity and expressions of BDNF and tight junction (TJ) proteins (occludin, ZO-1, claudin-1, claudin-2) of the PI-IBS mice were investigated. Based on the results of animal studies, we further performed RT-PCR and Western blots to assess how BDNF stimulation and BDNF knockdown impacted TJ proteins in the ht-29 intestinal epithelial cells.
  
  
  RESULTS
  Water content of stools was significantly increased in the PI-IBS mice compared with controls. Colonic mucosa from the PI-IBS mice displayed epithelial barrier defects and exhibited increased protein expressions of BDNF and claudin-2 and decreased protein expressions of occludin, ZO-1 and claudin-1. Furthermore, a siRNA against BDNF in the ht-29 cells could effectively suppress BDNF gene and protein expressions, and subsequently reduce TJ gene and protein levels. When the ht-29 cells were incubated with different doses of exogenous BDNF, significant increases of occludin, ZO-1 and claudin-1 and decreases of claudin-2 protein were observed.
  
  
  CONCLUSIONS
  BDNF may play a role in regulating intestinal epithelial barrier via affecting the expression of TJ proteins.
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Y-B
authors.initials: YB
authors.lastname: Yu
authors.affiliation: Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.|Department of Gastroenterology, General Hospital of Puyang Oilfield, Puyang, China.
authors.forename: D-Y
authors.initials: DY
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Q-Q
authors.initials: QQ
authors.lastname: Qi
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: X
authors.initials: X
authors.lastname: Long
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: F-X
authors.initials: FX
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: X-L
authors.initials: XL
authors.lastname: Zuo
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D062725:Tight Junction Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D062725:Tight Junction Proteins
keywords: 
  BDNF
  ; 
  IBS
  ; intestinal barrier; tight junction proteins